Originally published online as doi:10.1189/jlb.0208109 on May 29, 2008
Published online before print May 29, 2008
(Journal of Leukocyte Biology. 2008;84:331-337.)
© 2008
by Society for Leukocyte Biology
Conditioning response to granulocyte colony-stimulating factor via the dipeptidyl peptidase IV-adenosine deaminase complex
Daniele Focosi*,1,2,
Richard Eric Kast
,1,
Sara Galimberti* and
Mario Petrini*
* Division of Hematology, Azienda Ospedaliera Santa Chiara, University of Pisa, Pisa, Italy; and
Department of Psychiatry, University of Vermont, Burlington, Vermont, USA
2 Correspondence: Division of Hematology, Azienda Ospedaliera Santa Chiara, University of Pisa, via Roma 56, 56100 Pisa, Italy. E-mail: dfocosi{at}fin.org
ABSTRACT
G-CSF is routinely used to mobilize hematopoietic stem cells
(HSCs) from bone marrow (BM) into peripheral blood before aphaeresis,
but HSC harvesting can be suboptimal. On the other hand, transplanted
HSCs sometimes fail to engraft a recipient BM microenvironment
when G-CSF is used after transplantation, as pushing-CSF will
push HSCs away from marrow. So, G-CSF action needs to be potentiated
by other drugs. Marrow stromal cells establish a local CXCL12
concentration gradient that is the primary homing signal for
HSCs. Pharmacological interventions that modify this gradient,
therefore, have potential to help HSC mobilization (by decreasing
CXCL12) and engraftment (by increasing CXCL12). CXCL12 inactivation
is primarily mediated by dipeptidyl peptidase-IV. We review
here the currently available drugs affecting this enzyme that
could be used in the clinic to achieve phase-specific help for
G-CSF.
Key Words: bone marrow • CXCL12 • DPP-IV • G-CSF • hematopoietic stem cells • gliptins • sitagliptin
INTRODUCTION
"All the business of war, and indeed all the business of life, is to endevour to find out what you don’t know by what you do: that’s what I called‘guess what was at the other side of the hill’ " (Duke of Wellington, 1769–1852).
Hematopoietic stem cell transplantation (HSCT) is useful in treating a wide range of neoplastic and non-neoplastic conditions: Peripheral blood HSCT has many advantages over bone marrow (BM) explant, being less invasive and painful for the donor/patient and inducing less graft-versus-host disease in the recipient in the allogeneic setting.
HSC mobilization from BM to peripheral blood mimics enhancement of the physiological release of HSC and progenitor cells in response to stress signals during injury and inflammation. Recombinant human (rh)G-CSF is currently the gold standard for HSC mobilization in many cancer populations, but this drug doesn’t work in a significant number of patients who are denied potentially curative, high-dose chemotherapies requiring HSC support. Some aspects of G-CSF-assisted HSC mobilization failure are thought to be a result of G-CSF short half-life and receptor occupancy, so higher doses and glycosylated [1
] and pegylated [2
] isoforms have been introduced into the clinic with some promising results. Anyway, they also may fail to achieve the required HSC mobilization, and the accompanying greater granulocytosis may have side effects [3
].
In the setting of autologous HSCT, failures to mobilize enough HSCs on G-CSF remain between 10% and 30% depending on underlying disease, and heavily pretreated patients have higher harvest failure rates. To address these problems with harvest phase, new agents are being tried that act on the primary homing signal for HSC, the CXCL12-CXCR4-matrix metalloproteinase 9 (MMP9) pathway, as first shown by Tsvee Lapidot Laboratories at the Weizmann Institute (Israel) [4
]. In brief, here, the up-regulation of neutrophil MMP9 (a.k.a., gelatinase B) alters the stoichiometry between pro-MMP9 and tissue inhibitor of metalloproteinase-1, resulting in MMP9 activation [5
], cleavage of membrane stem cell factor (SCF) [6
], and finally, release of HSCs from BM stroma. Examples of G-CSF-synergic agents for mobilization include rhSCF [7
], human growth hormone [8
], CpG-oligodeoxynucleotides [9
], IL-8 [10
], antibodies against the β-2 integrins LFA-1 and membrane-activated complex 1 [11
], growth-related oncogene-β (a.k.a., CXCL2) [12
], or CXCR4 antagonists such as AMD3100, CTCE-0021 [13
], and analogs [14
]. Furthermore, promising preclinical results have been reported for osteogenic growth peptide 10-14 [15
, 16
], parathyroid hormone [17
], CXCL2 [5
] and analogs [12
], CXCL8 [18
] (which is potentiated tenfold after aminoterminal processing by MMP9 [19
]), placental growth factor [20
], anti-VLA4 antibodies [21
], the cleaved forms of soluble urokinase receptor [22
], and induction of CXCL12 plasma elevation using viral vectors [23
]. In this way, patients who previously failed can then successfully collect enough HSCs for transplantation, and others can collect more HSCs in fewer apheretic sessions.
Anyway, even these combination strategies often fail [24
] or harvest HSC that exhibit reduced engraftment potential [25
]. Better mobilization strategies are still needed to avoid use of the potentially harmful chemotherapy/cytokine combinations or direct BM donation, especially for healthy donors of HSCs for allogeneic transplantation.
On the other side of the HSCT process, transplanted HSCs occasionally fail to colonize and thrive in the recipient BM, often independently from the dose of reinfused CD34+ HSCs. Such engraftment failure accounts for 10% of readmission to the hospital of HSCT recipients [26
].
Recent research data about the bimolecular complex of dipeptidyl peptidase-IV (DPP-IV) and adenosine deaminase (ADA) indicate that currently marketed drugs can now manipulate the CXCL12-CXCR4 axis to improve both phases of G-CSF treatment (harvest and engraftment), potentially improving the overall HSCT success rate.
G-CSF IN BM HSC MOBILIZATION
G-CSF has many independent effects on hematopoiesis, not only
on homing but also on proliferation and differentiation. It
is useful to think of HSCT as two distinct phases, both using
G-CSF but each requiring different pharmacologic treatment to
constructively shape the G-CSF response. During HSC harvesting,
G-CSF is used to mobilize HSCs from BM to peripheral blood.
After HSCT, the goal is encouraging HSC homing to BM and engraftment.
THE CXCL12-CXCR4 AXIS
CXCL12 (a.k.a., stromal cell-derived factor 1
) is a chemokine,
preeminently synthesized and released by fibroblasts and osteoblasts
[
27
] but also by other BM cells. Its cognate receptor CXCR4
is expressed on HSCs and neutrophils, where expression is up-regulated
by NO [
28
].
Among other signals, HSC homing to BM is driven by a CXCL12 concentration gradient [4
]. Interestingly, G-CSF suppresses CXCL12 expression throughout BM but particularly in osteoblasts [27
, 29
, 30
] and also up-regulates catabolic destruction of active CXCL12 (see below). Both of these effects result in HSC egress from BM (Fig. 1
).
G-CSF treatment also induces sharp increases in osteoblast expression
and secretion of DPP-IV [
27
,
31
], which by inactivating CXCL12
[
27
,
30
31
32
33
34
], is believed to reduce the chemotactic
gradient to BM, followed by HSCs. Increased circulation of HSC
(and the accompanying neutrophilia) is seen as the consequence.
DPP-IV
DPP-IV (EC 3.4.14.5), also known as CD26, is a membrane-bound,
110-kDa exopeptidase. It performs the initial and quantitatively
primary, catabolic step in inactivation of CXCL12. DPP-IV is
an ectoenzyme frequently present on the apical surface of epithelial
cells [
35
], and after cleavage, it is also found in connective
tissue cells [
36
] {in soluble form and/or associated with the
surrounding extracellular matrix (ECM) [
37
]}, maintaining the
same catalytic efficiency [
38
]. The cysteine-rich region of
DPP-IV contains fibronectin and collagen-binding sites, and
the released enzyme can secondarily associate with the ECM,
potentially generating gradients or focal microenvironments
with specific enzyme activity [
39
]. DPP-IV is a highly sialylated
glycoprotein, and inactivation of a single N-glycosylation site
results in changes of enzymatic activity, subcellular localization,
and biological stability of the protein [
40
,
41
].
DPP-IV is expressed in several tissues, with high levels in a subpopulation of CD34+ HSCs isolated from cord blood [42
], kidneys [43
], and small intestine and lower levels in lungs, liver, and spleen [44
]. It is also found on Hodgkin’s lymphomas, anaplastic lymphoma kinase-positive anaplastic, large cell lymphomas [45
], and some T cell non-Hodgkin’s lymphomas [46
]. DPP-IV spontaneously forms homodimers on the outer cell membrane of cells on which it is expressed [30
].
Within the hematopoietic environment, DPP-IV is located in specialized microdomains on membranes of the connective tissue cells, called lipid rafts. Such rafts provide the molecular environment required for optimal enzyme activity.
DPP-IV was originally known as a T cell differentiation or activation marker [47
], associating with CD45 and increasing tyrosine phosphorylation in signal transduction pathways, including activation of MAPK [48
, 49
]. In addition to the control of activation and proliferation of T cells, DPP-IV has a costimulating activity for granulocytes and macrophages [50
]. Inhibition of the DPP-IV enzymatic activity was reported to increase granulocyte-macrophage colony formation as well as immature thymocyte proliferation. These data contrast anyway with the reported increase of IL-2 production associated with increased DPP-IV activity in mitogen-stimulated T cells and the decrease of IL-2 production and antigen-stimulated proliferation of peripheral T cells caused by DPP-IV inhibitors [51
]. Biological activities that have been proposed for DPP-IV include degradation of denatured collagen, intestinal and renal handling of proline-containing peptides, as well as metabolism of neuropeptides and glucagon-like peptides (GLPs) [51
, 52
].
DPP-IV recognizes and removes the two N-terminal amino acids of proteins with a penultimate proline or less efficiently, a penultimate alanine. Many cytokines involved in hematopoiesis (such as IL-1β, IL-2, IL-3, IL-5, IL-6, IL-8, IL-10, IL-13, erythropoietin, GM-CSF, and G-CSF itself) contain the DPP-IV-susceptible N-terminal amino acid sequence with proline in the second position. Anyway, Hoffmann et al. [53
] found no degradation for the intact recombinant cytokines IL-1, IL-1β, IL-2, and G-CSF and for natural IL-2.
Recent studies have shown that the biological activities of chemokines can be regulated by the DPP-IV-mediated cleavage of their N-terminal region [54
55
56
]. Among its targets, DPP-IV readily cleaves the N-terminal amino acids of CXCL12, rendering it no longer chemotactic for HSCs [31
, 33
, 42
]. Although CXCL12 catabolism can also be mediated by many different serine proteases, such as cathepsins K [57
] and G [58
], and neutrophil elastase [59
], DPP-IV is by far the most studied. Furthermore, in response to G-CSF administration, CXCR4 is also cleaved by an unknown serine protease, completing disruption of this signaling pathway [58
, 60
]. Also, at the same time in the BM, G-CSF induces down-regulation of the serine protease inhibitors A1 and A3 (SERPINA1 and SERPINA3, respectively) [61
]. Truncated by DPP-IV, CXCL12 is no longer a chemotactic signal for neutrophils or HSCs and actually acts as an antagonist, resulting in the reduction of a migratory response to normal CXCL12 [62
]. Accordingly, inhibiting the endogenous DPP-IV activity on CD34+ HSCs enhances the migratory response of these cells to CXCL12 [42
].
The group of Cristopherson et al. [33
] has shown that inhibition (with diprotin A) or deletion of DPP-IV on infused murine HSCs greatly increases donor-cell contribution to peripheral blood leukocytes, suggesting that improvement of HSCT efficiency may be possible in the clinic. Short-term in vitro G-CSF and GM-CSF treatment up-regulates DPP-IV, resulting in down-regulation of the functional ability of CD34+CD38– cells to respond to CXCL12 [31
]. The authors suggested that the use G-CSF and GM-CSF may have unforeseen, detrimental effects on the trafficking of HSC during HSCT, which could be overcome through the use of DPP-IV inhibitors [31
].
On the other side, mice treated with DPP-IV inhibitors during G-CSF-induced mobilization showed a reduction in the number of HSCs in peripheral blood as compared with the G-CSF regimen alone [62
]. Similary, the number of HPCs detected in G-CSF-treated DPP-IV–/– mouse peripheral blood was significantly lower than in G-CSF-treated wild-type mouse peripheral blood after a 2- or 4-day G-CSF regimen [63
].
G-CSF treatment ultimately results in neutrophil and HSC up-regulation of CXCR4 [34
] with consequent increased homing to extramedullary sites that may retain CXCL12 expression [64
]. Indiscriminate homing directed to an extramedullary site that does not have their CXCL12 down-regulated by G-CSF is finally counterproductive during both phases of HSCT—harvest and engraftment.
DPP/ADA COMPLEX
ADA (EC 3.5.4.4) is a 41-kDa soluble, monomeric enzyme catalyzing
deamination of adenosine to inosine and ammonia [
65
]. Membrane-bound
ADA has significantly higher catalytic efficiency than the soluble
form. Interestingly, membrane-bound DPP-IV is a high-affinity
receptor for ADA [
66
,
67
]. Binding to ADA does not require
the catalytic domain of DPP-IV and doesn’t induce enzymatic
or conformational changes. This pair of enzymes is involved
in immunoregulatory mechanisms through the control of adenosine-mediated
inhibition of lymphocyte IL-2 production and proliferation [
68
].
Autosomal, recessive mutations that cause a loss of function
in ADA, which in turn impair lymphocyte differentiation, cause
a subtype of SCID (ADA-SCID) that can be treated by replacement
therapy with pegylated ADA protein, allogeneic HSCT, or HSC-targeted
gene therapy [
69
].
Of interest, the optimal pH for DPP is higher than the normal, extracellular pH [70
], values usually not found in intracellular space and even less in infected or actively inflamed tissues, where the pH tends to go below normal. By locally generating ammonia, ADA raises the local pH and increases DPP-IV efficiency. In fact, DPP-IV-bound ADA activity has 1000-fold greater activity than free ADA [30
]. Thus, a coral-like molecular symbiosis arises [30
].
We propose here that this bimolecular complex is important in HSC mobilization (by functioning vigorously and well) and in HSC engraftment in the BM after transplantation (by inhibition).
So how can we use this understanding to improve G-CSF use during HSCT?
CURRENT PHARMACOLOGICAL OPTIONS
During HSC harvesting, homing to BM needs to be inhibited; on
the contrary, homing to BM is needed during HSC engraftment.
Some options are available, and they are summarized in
Table 1
.
View this table:
[in this window]
[in a new window]
|
Table 1. Drugs That Should Be Used During HSC Mobilization from BM and Drugs That Should Be Used to Help HSC Engraftment after Transplantation
|
ADA can be weakly inhibited by methotrexate [
64
], which is
currently used as an immunosuppressive drug in allogeneic HSCT
with myeloablative conditioning (generally 5–10 mg/m
2 on Days 1, 3, 6, and 11 post-transplant). ADA is also potently
inhibited by purine nucleoside analogs, including cladribine
[
85
,
86
], pentostatin [
88
], and fludarabine [
87
]. Of interest,
it is a common finding that chronic lymphocytic, leukemia patients,
previously treated with fludarabine, are highly refractory to
G-CSF-induced HSC mobilization [
90
], and the same is true for
patients with acute myeloid leukemia treated with intensified
induction/consolidation protocols containing fludarabine [
91
].
These clinical evidences fit well with our suggestion that ADA
inhibition facilitates HSC retention in BM.
On the contrary, dipyridamole is occasionally mentioned as an inhibitor of ADA, but actually, it increases extracellular ammonia generated by ADA. Circulating levels of adenosine are increased after dipyridamole [81
], increasing the ADA substrate available for generation of ammonia in vivo in mice [82
], dogs [83
], and humans [84
].
On the other side of the bimolecular complex, expression of DDP-IV is induced by retinoic acid [71
72
73
] and IFNs [73
, 74
]. By reverse, DPP-IV inhibition with the tripeptide diprotin A (Ile-Pro-Ile) has already been shown to improve HSC homing and increase engraftment efficiency in murine models of HSCT [92
]. Confirming that this pathway is important for homing to the primary hematopoietic organs at any definite age, DPP-IV inhibition increases donor cell homing to the fetal liver and improves allogeneic engraftment following in utero HSCT [93
]. Interestingly, DPP-IV inhibition also appears beneficial for solid organ transplantation, indicating putative, immunoregulatory actions. In experimental cardiac allograft transplantation in rats, acute rejection was associated with increased serum DPP-IV activity: Inhibition of DPP-IV with proprodiphenyl phosphonate abrogated acute and accelerated rejection, impairing cytotoxicity and allospecific Ig synthesis. Furthermore, human recipients of kidney transplants displayed a significant drop in DPP-IV expression on peripheral blood leukocytes for up to 18 months postoperatively (P<0.001) [94
].
"Gliptins" are a class of selective DPP-IV inhibitors that help lower postprandial glucose by inhibiting the breakdown of GLP-1 [95
] and have proved useful to treat noninsulin-dependent diabetes mellitus (NIDDM). Sitagliptin phosphate (previously named MK-0431 and finally marketed as Januvia®) [76
] is an oral agent recently introduced to the U.S. market, and other related agents such as vildagliptin (previously named LAF-237 and finally marketed as Galvus®) and saxagliptin (previously named BMS-477118) will be introduced soon. Although its name suggests glucagon-like activity, GLP-1 has a reverse-from-glucagon effect on pancreatic β cells: Actually, GLP-1 stimulates insulin secretion. By lowering destruction of active GLP-1 by DPP-IV, gliptins increase postprandial insulin and consequentially lower postprandial glucose. Interestingly, metformin, a different, older drug for treating NIDDM, works by several paths: Weak inhibition of DPP-IV is one of them, although not its central effect. One week using metformin at 1 g daily modestly decreases soluble DPP-IV activity in humans with diabetes [77
], and 14 days using metformin lowered DPP-IV activity in diabetic Zucker rats [96
], and obese diabetic mice [76
].
Lithium is another drug well known for its HSC-mobilizing effects [75
]. Of interest, lithium induces weight gain by increasing insulin sensitivity [97
]: This link to the insulin-sensitizing activity of DPP-IV inhibitors leads to the conjecture that both of these effects of lithium could arise by DPP-IV up-regulation, which remains to be investigated.
Some of the predictions of the main thesis of this paper have already been tested in the clinic. For example, increased extracellular adenosine given during G-CSF mobilization of HSC and neutrophils increases harvest in mice beyond that obtained with G-CSF alone [82
, 98
, 99
.
ADA-SCID patients undergoing allogeneic HSCT successfully engraft without prior cytoreductive conditioning [100
], consistent with the requirement for ADA inhibition in HSC engraftment, although restoration of immune function occurs by rescue of endogenous, ADA-deficient lymphocytes through cross-correction from the engrafted, ADA-repleted donor cells [101
]. On the contrary, the same patients fail G-CSF-induced HSC mobilization [102
], consistent with the requirement for ADA activity.
CONCLUSIONS AND PERSPECTIVES
None of the suggested pharmacological interventions has been
tested in HSCT to date. They are all of varying degrees of conjecture
and must be subject to careful trials before use. Lithium is
the suggested drug with the most research data in humans supporting
its use in HSCT. We believe gliptins are the drug category most
likely to be of benefit. Anyway, both have extremely low potential
for toxicity.
During G-CSF-induced mobilization of HSCs from BM, stimulation and avoidance of inhibition of the DPP-IV-ADA complex are desirable. As can be expected from the symbiotic relationship between the two molecules, inhibiting DPP-IV and ADA will maximize total DPP-IV inhibition. As DPP-IV is the catalytic element that is up-regulated by G-CSF to increase CXCL12 degradation [103
], depriving HSCs and neutrophil lineage cells of their central chemokine for BM homing should reasonably lead to better HSC mobilization. Adenosine could be given i.v. at this stage, and on the contrary, eventual gliptins and metformin should be discontinued.
During HSC engraftment, maximum inhibition of the DPP-IV-ADA complex will be desirable. This can currently be done by inhibition of ADA with pentostatin, cladribrine, and/or gliptins: the less DPP-IV activity, the less CXCL12 breakdown, and the stronger the homing signal for the transplanted HSC.
Our institution is currently running two unsponsored phase I/II clinical trials of sitagliptin, 100 mg orally, two/day, in multiple myeloma patients undergoing high-dose melphalan (100 mg/m2) supported by autologous HSCT, with or without G-CSF adjunct.
Similarly, sitagliptin could be of some use in the allogeneic HSCT settings, especially in patients experiencing delayed graft failure, as supported by a recent case report [104
]. Still, in the allogeneic setting, maneuvers that encourage engraftments are needed in cord blood transplantation to reduce infective episodes [105
].
Some concerns still remain. Regulatory T lymphocytes also use the CXCL12/CXCR4 pathway to home to the BM [106
]. Their mobilization to periphery (or retention in BM) by these pharmacologic maneuvers could have unpredictable, potentially negative consequences. Careful study of each suggested intervention to the DDP-ADA pathway will be necessary.
FOOTNOTES
These authors contributed equally to this manuscript.
Received February 14, 2008;
revised April 16, 2008;
accepted April 20, 2008.
REFERENCES
1 - Hoglund, M., Smedmyr, B., Bengtsson, M., Totterman, T., Cour-Chabernaud, V., Yver, A., Simonsson, B. (1997) Mobilization of CD34+ cells by glycosylated and nonglycosylated G-CSF in healthy volunteers—a comparative study Eur. J. Haematol. 59,177-183[Medline]
2 - Malerba, L., Mele, A., Leopardi, G., Stramigioli, S., Politi, P., Visani, G. (2006) Pegfilgrastim effectively mobilizes PBSC in a poor mobilizer multiple myeloma patient Eur. J. Haematol. 76,436-439[CrossRef][Medline]
3 - Togel, F., Isaac, J., Westenfelder, C. (2004) Hematopoietic stem cell mobilization-associated granulocytosis severely worsens acute renal failure J. Am. Soc. Nephrol. 15,1261-1267[Abstract/Free Full Text]
4 - Peled, A., Petit, I., Kollet, O., Magid, M., Ponomaryov, T., Byk, T., Nagler, A., Ben-Hur, H., Many, A., Shultz, L., Lider, O., Alon, R., Zipori, D, Lapidot, T. (1999) Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4 Science 283,845-848[Abstract/Free Full Text]
5 - Pelus, L., Fukuda, S. (2006) Peripheral blood stem cell mobilization: the CXCR2 ligand GROβ rapidly mobilizes hematopoietic stem cells with enhanced engraftment properties Exp. Hematol. 34,1010-1020[CrossRef][Medline]
6 - Heissig, B., Hattori, K., Dias, S., Friedrich, M., Ferris, B., Hackett, N. R., Crystal, R. G., Besmer, P., Lyden, D., Moore, M. A., Werb, Z., Rafii, S. (2002) Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand Cell 109,625-637[CrossRef][Medline]
7 - Dawson, M., Schwarer, A., Muirhead, J., Bailey, M., Bollard, G., Spencer, A. (2005) Successful mobilization of peripheral blood stem cells using recombinant human stem cell factor in heavily pretreated patients who have failed a previous attempt with a granulocyte colony-stimulating factor-based regimen Bone Marrow Transplant. 36,389-396[CrossRef][Medline]
8 - Carlo-Stella, C., Di Nicola, M., Milani, R., Guidetti, A., Magni, M., Milanesi, M., Longoni, P., Matteucci, P., Formelli, F., Ravagnani, F., Corradini, P., Gianni, A. M. (2004) Use of recombinant human growth hormone (rhGH) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) for the mobilization and collection of CD34+ cells in poor mobilizers Blood 103,3287-3295[Abstract/Free Full Text]
9 - Nardini, E., Morelli, D., Aiello, P., Besusso, D., Calcaterra, C., Mariani, L., Palazzo, M., Vecchi, A., Paltrinieri, S., Menard, S., Balsari, A. (2005) CpG-oligodeoxynucleotides induce mobilization of hematopoietic progenitor cells into peripheral blood in association with mouse KC (IL-8) production J. Cell. Physiol. 204,889-895[CrossRef][Medline]
10 - Watanabe, T., Kawano, Y., Kanamaru, S., Onishi, T., Kaneko, S., Wakata, Y., Nakagawa, R., Makimoto, A., Kuroda, Y., Takaue, Y., Talmadge, J. (1999) Endogenous interleukin-8 (IL-8) surge in granulocyte colony-stimulating factor-induced peripheral blood stem cell mobilization Blood 93,1157-1163[Abstract/Free Full Text]
11 - Velders, G., Pruijt, J., Verzaal, P., van Os, R., van Kooyk, Y., Figdor, C., de Kruijf, E., Willemze, R., Fibbe, W. E. (2002) Enhancement of G-CSF-induced stem cell mobilization by antibodies against the β 2 integrins LFA-1 and Mac-1 Blood 100,327-333[Abstract/Free Full Text]
12 - King, A. G., Horowitz, D., Dillon, S. B., Levin, R., Farese, A. M., MacVittie, T. J., Pelus, L. M. (2001) Rapid mobilization of murine hematopoietic stem cells with enhanced engraftment properties and evaluation of hematopoietic progenitor cell mobilization in rhesus monkeys by a single injection of SB-251353, a specific truncated form of the human CXC chemokine GRO{β} Blood 97,1534-1542[Abstract/Free Full Text]
13 - Pelus, L., Bian, H., Fukuda, S., Wong, D., Merzouk, A., Salari, H. (2005) The CXCR4 agonist peptide, CTCE-0021, rapidly mobilizes polymorphonuclear neutrophils and hematopoietic progenitor cells into peripheral blood and synergizes with granulocyte colony-stimulating factor Exp. Hematol. 33,295-307[CrossRef][Medline]
14 - Martin, C., Bridger, G., Rankin, S. (2006) Structural analogues of AMD3100 mobilize hematopoietic progenitor cells from bone marrow in vivo according to their ability to inhibit CXCL12 binding to CXCR4 in vitro Br. J. Haematol. 134,326-329[CrossRef][Medline]
15 - Fazzi, R., Testi, R., Trasciatti, S., Galimberti, S., Rosini, S., Piras, F., L'Abbate, G., Conte, A., Petrini, M. (2002) Bone and bone-marrow interactions: haematological activity of osteoblastic growth peptide (OGP)-derived carboxy-terminal pentapeptide. Mobilizing properties on white blood cells and peripheral blood stem cells in mice Leuk. Res. 26,19-27[CrossRef][Medline]
16 - Fazzi, R., Galimberti, S., Testi, R., Pacini, S., Trasciatti, S., Rosini, S., Petrini, M. (2002) Bone and bone marrow interactions: hematological activity of osteoblastic growth peptide (OGP)-derived carboxy-terminal pentapeptide. II. Action on human hematopoietic stem cells Leuk. Res. 26,839-848[CrossRef][Medline]
17 - Ballen, K., Shpall, E., Avigan, D., Yeap, B., Fisher, D., McDermott, K., Dey, B., Attar, E., McAfee, S., Konopleva, M., Antin, J., Spitzer, T. (2007) Phase I trial of parathyroid hormone to facilitate stem cell mobilization Biol. Blood Marrow Transplant. 13,838-843[CrossRef][Medline]
18 - Fibbe, W., Pruijt, J., Velders, G. A., Opdenakker, G., van Kooyk, Y., Figdor, C., Willemze, R. (1999) Biology of IL-8-induced stem cell mobilization Ann. N. Y. Acad. Sci. 872,71-82[CrossRef][Medline]
19 - Van den Steen, P., Proost, P., Wuyts, A., Van Damme, J., Opdenakker, G. (2000) Neutrophil gelatinase B potentiates interleukin-8 tenfold by aminoterminal processing, whereas it degrades CTAP-III, PF-4, and GRO- and leaves RANTES and MCP-2 intact Blood 96,2673-2681[Abstract/Free Full Text]
20 - Carlo-Stella, C., Di Nicola, M., Longoni, P., Cleris, L., Lavazza, C., Milani, R., Milanesi, M., Magni, M., Pace, V., Colotta, F., Avanzini, M., Formelli, F., Gianni, A. (2007) Placental growth factor-1 potentiates hematopoietic progenitor cell mobilization induced by granulocyte colony-stimulating factor in mice ad nonhuman primates Stem Cells 25,252-261[CrossRef][Medline]
21 - Papayannopoulou, T., Nakamoto, B. (1993) Peripheralization of hemopoietic progenitors in primates treated with anti-VLA4 integrin Proc. Natl. Acad. Sci. USA 90,9374-9378[Abstract/Free Full Text]
22 - Selleri, C., Montuori, N., Ricci, P., Visconte, V., Baiano, A., Carriero, M. V., Rotoli, B., Rossi, G., Ragno, P. (2006) In vivo activity of the cleaved form of soluble urokinase receptor: a new hematopoietic stem/progenitor cell mobilizer Cancer Res. 66,10885-10890[Abstract/Free Full Text]
23 - Hattori, K., Heissig, B., Tashiro, K., Honjo, T., Tateno, M., Shieh, J-H., Hackett, N. R., Quitoriano, M. S., Crystal, R. G., Rafii, S., Moore, M. A. S. (2001) Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells Blood 97,3354-3360[Abstract/Free Full Text]
24 - da Silva, M., Pimentel, P., Carvalhais, A., Barbosa, I., Machado, A., Campilho, F., Sousa, S., Miranda, N., da Costa, F., Campos, A., Vaz, C., Antas, J., Passos-Coehlho, J. (2004) Ancestim (recombinant human stem cell factor, SCF) in association with filgrastim does not enhance chemotherapy and/or growth factor-induced peripheral blood progenitor cell (PBPC) mobilization in patients with a prior insufficient PBPC collection Bone Marrow Transplant. 34,683-691[CrossRef][Medline]
25 - Mueller, Y., Cramer, D., Huang, Y., Exner, B., Ildstad, S. (2002) Hematopoietic stem cells from the marrow of mice treated with Flt3 ligand are significantly expanded but exhibit reduced engraftment potential Transplantation 73,1177-1185[CrossRef][Medline]
26 - Moya, R., Espigado, I., Parody, R., Carmona, M., Marquez, F., De Blas, J. (2006) Evaluation of readmissions in hematopoietic stem cell transplant recipients Transplant. Proc. 38,2591-2592[CrossRef][Medline]
27 - Semerad, C., Christopher, M., Liu, F., Short, B., Simmons, P., Winkler, I., Levesque, J., Chappel, J., Ross, F., Link, D. (2005) G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow Blood 106,3020-3027[Abstract/Free Full Text]
28 - Zhang, Y., Wittner, M., Bouamar, H., Harrier, P., Vainchenker, W., Louache, F. (2007) Identification of CXCR4 as a new nitric oxide-regulated gene in human CD34+ cells Stem Cells 25,211-219[CrossRef][Medline]
29 - Semerad, C., Liu, F., Gregory, A., Stumpf, K., Link, D. (2002) G-CSF is an essential regulator of neutrophil trafficking from the bone marrow to the blood Immunity 17,413-423[CrossRef][Medline]
30 - Link, D. (2005) Neutrophil homeostasis: a new role for stromal cell-derived factor-1 Immunol. Res. 32,169-178[CrossRef][Medline]
31 - Christopherson, K. W., II, Uralil, S., Porecha, N. K., Zabriskie, R. C., Kidd, S., Ramin, S. (2006) G-CSF- and GM-CSF-induced upregulation of CD26 peptidase downregulates the functional chemotactic response of CD34+CD38- human cord blood hematopoietic cells Exp. Hematol. 34,1060-1068[CrossRef][Medline]
32 - Winkler, I., Levesque, J. (2006) Mechanisms of hematopoietic stem cell mobilization: when innate immunity assails the cells that make blood and bone Exp. Hematol. 34,996-1009[CrossRef][Medline]
33 - Christopherson, K. W., II, Hangoc, G., Mantel, C., Broxmeyer, H. (2004) Modulation of hematopoietic stem cell homing and engraftment by CD26 Science 305,1000-1003[Abstract/Free Full Text]
34 - Petit, I., Szyper-Kravitz, M., Nagler, A., Lahav, M., Peled, A., Habler, L., Ponomaryov, T., Taichman, R., Arenzana-Seisdedos, F., Fujii, N., Sandbank, J., Zipori, D, Lapidot, T. (2002) G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4 Nat. Immunol. 3,687-694[CrossRef][Medline]
35 - Tsugiki, M., Kobayashi, Y., Kawasaki, T., Yoshimi, T. (1998) Identification of bile canalicular cell surface antigen HAM.4 as dipeptidyl peptidase IV (DPPIV) and characterization of its role in hepatic regeneration after partial hepatectomy in rats Dig. Dis. Sci. 43,2591-2600[CrossRef][Medline]
36 - Iwaki-Egawa, S., Watanabe, Y., Fujimoto, Y. (1998) Dipeptidyl peptidase IV from human serum: purification, characterization, and N-terminal amino acid sequence J. Biochem. 124,428-433[Abstract/Free Full Text]
37 - Levy, M., McCoughan, G. W., Abbott, C. A., Park, J., Cunningham, A., Müller, E. R., Rettig, W. J., Gorrell, M. (1999) Fibroblast activation protein: a cell surface dipeptidyl peptidase and gelatinase expressed by stellate cells at the tissue remodeling interface in human cirrhosis Hepatology 29,1768-1778[CrossRef][Medline]
38 - Pereira, D., Gomes, L., El-Cheikh, M., Borojevic, R. (2003) Dipeptidyl peptidase IV (CD26) activity in the hematopoietic system: differences between the membrane-anchored and the released enzyme activity Braz. J. Med. Biol. Res. 36,567-578[Medline]
39 - Löster, K., Zeilinger, K., Schuppan, D, Reutter, W. (1995) The cysteine-rich region of dipeptidyl peptidase IV (CD26) is the collagen-binding site Biochem. Biophys. Res. Commun. 217,341-348[CrossRef][Medline]
40 - Fan, H., Meng, W., Kilian, C., Grams, S., Reutter, W. (1997) Domain-specific N-glycosylation of the membrane glycoprotein dipeptidylpeptidase IV (CD26) influences its subcellular trafficking, biological stability, enzyme activity and protein folding Eur. J. Biochem. 246,243-251[Medline]
41 - Smith, R., Talhouk, J., Brown, E., Edgar, S. (1998) The significance of hypersialylation of dipeptidyl peptidase IV (CD26) in the inhibition of its activity by tat and other cationic peptides. CD26: a subverted adhesion molecule for HIV peptide binding AIDS Res. Hum. Retroviruses 14,851-868[Medline]
42 - Christopherson, K. W., II, Hangoc, G., Broxmeyer, H. E. (2002) Cell surface peptidase CD26/dipeptidylpeptidase IV regulates CXCL12/stromal cell-derived factor-1{}-mediated chemotaxis of human cord blood CD34+ progenitor cells J. Immunol. 169,7000-7008[Abstract/Free Full Text]
43 - Hopsu-Havu, V., Glaner, G. (1966) A new dipeptide naphthylamidase hydrolyzing glycyl-prolyl-β-naphthylamide Histochimie 7,197-201[CrossRef][Medline]
44 - Hong, W., Petell, J., Swank, D., Sanford, J., Hixson, D. C., Doyle, D. (1989) Expression of dipeptidyl peptidase IV in rat tissues is mainly regulated at the mRNA levels Exp. Cell Res. 182,256-266[CrossRef][Medline]
45 - Kameoka, J., Ichinohasama, R., Inoue, H., Yamamoto, J., Yokoyama, H., Tomiya, Y., Yamada, M., Ishizawa, K., Harigae, H., Sawai, T., Sasaki, T. (2006) CD26, together with cell surface adenosine deaminase, is selectively expressed on ALK-positive, but not on ALK-negative, anaplastic large cell lymphoma and Hodgkin’s lymphoma Leuk. Lymphoma 47,2181-2188[CrossRef][Medline]
46 - Carbone, A., Cozzi, M., Gloghini, A., Pinto, A. (1994) CD26/dipeptidyl peptidase IV expression in human lymphomas is restricted to CD30-positive anaplastic large cell and a subset of T-cell non-Hodgkin’s lymphomas Hum. Pathol. 25,1360-1365[CrossRef][Medline]
47 - Hegen, M., Niedobitek, G., Klein, C. E., Stein, H., Fleischer, B. (1990) The T cell triggering molecule Tp103 is associated with dipeptidyl aminopeptidase IV activity J. Immunol. 144,2908-2914[Abstract]
48 - Torimoto, Y., Dang, N., Vivier, E., Tanaka, T., Schlossman, S., Morimoto, C. (1991) Coassociation of CD26 (dipeptidyl peptidase IV) with CD45 on the surface of human T lymphocytes J. Immunol. 147,2514-2517[Abstract/Free Full Text]
49 - Hegen, M., Kameoka, J., Dong, R. P., Schlossman, S. F., Morimoto, C. (1997) Cross-linking of CD26 by antibody induces tyrosine phosphorylation and activation of mitogen-activated protein kinase Immunology 90,257-264[CrossRef][Medline]
50 - Bristol, L., Sakaguchi, K., Appella, E., Doyle, D., Takács, L. (1992) Thymocyte costimulating antigen is CD26 (dipeptidyl-peptidase IV): co-stimulation of granulocyte, macrophage, and T lineage cell proliferation via CD26 J. Immunol. 149,367-372[Abstract]
51 - Holst, J., Deacon, C. (1998) Inhibition of the activity of dipeptidyl-peptidase IV as a treatment for type 2 diabetes Diabetes 47,1663-1670[Abstract]
52 - Augustyns, K., Bal, G., Thonus, G., Belyaev, A., Zhang, X., Bollaert, W., Lambier, A., Durinx, C., Goossens, F., Haemers, A. (1999) The unique properties of dipeptidyl-peptidase IV (DPP IV/CD26) and the therapeutic potential of DPP IV inhibitors Curr. Med. Chem. 6,311-327[Medline]
53 - Hoffmann, T., Faust, J., Neubert, K., Ansorge, S. (1993) Dipeptidyl peptidase IV (CD 26) and aminopeptidase N (CD 13) catalyzed hydrolysis of cytokines and peptides with N-terminal cytokine sequences FEBS Lett. 336,61-64[CrossRef][Medline]
54 - Oravecz, T., Pall, M., Roderiquez, G., Gorrell, M., Ditto, M., Nguyen, N., Boykins, R., Unsworth, E., Norcross, M. (1997) Regulation of the receptor specificity and of the function of the chemokine RANTES by dipeptidyl peptidase IV (CD-26)-mediated cleavage J. Exp. Med. 186,1865-1872[Abstract/Free Full Text]
55 - Van Coillie, E., Proost, P., Van Aelst, I., Struyf, S., Polfliet, M., De Meester, I., Harvey, D. J., Van Damme, J., Opendakker, G. (1998) Functional comparison of two human monocyte chemotatic protein-2 isoforms, roles of the amino-terminal pyroglutamic acid and processing by CD26/dipeptidyl peptidase IV Biochemistry 37,12672-12680[CrossRef][Medline]
56 - Lambier, A., Proost, P., Durinx, C., Bal, G., Senten, K., Augustyns, K., Schrape, S., Van Damme, J., De Meester, I. (2001) Kinetic investigation of chemokine truncation by CD26/dipeptidyl peptidase IV reveals a striking selectivity within the chemokine family J. Biol. Chem. 276,29839-29845[Abstract/Free Full Text]
57 - Kollet, O., Dar, A., Shivtiel, S., Kalinkovich, A., Lapid, K., Sztainberg, Y., Tesio, M., Samstein, R. M., Goichberg, P., Spiegel, A, Elson, A., Lapidot, T. (2006) Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells Nat. Med. 12,657-664[CrossRef][Medline]
58 - Levesque, J-P., Hendy, J., Takamatsu, Y., Simmons, P. J., Bendall, L. J. (2003) Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide J. Clin. Invest. 111,187-196[CrossRef][Medline]
59 - Rao, R., Betz, T., Lamont, D., Kim, M., Shaw, S., Froio, R., Baleux, F., Arenzana-Seisdedos, F., Alon, R., Luscinskas, F. (2004) Elastase release by transmigrating neutrophils deactivates endothelial-bound SDF-1 and attenuates subsequent T lymphocyte transendothelial migration J. Exp. Med. 200,713-724[Abstract/Free Full Text]
60 - Kim, H. K., De La Luz Sierra, M., Williams, C. K., Gulino, A. V., Tosato, G. (2006) G-CSF down-regulation of CXCR4 expression identified as a mechanism for mobilization of myeloid cells Blood 108,812-820[Abstract/Free Full Text]
61 - Winkler, I. G., Hendy, J., Coughlin, P., Horvath, A., Levesque, J-P. (2005) Serine protease inhibitors serpina1 and serpina3 are down-regulated in bone marrow during hematopoietic progenitor mobilization J. Exp. Med. 201,1077-1088[Abstract/Free Full Text]
62 - Christopherson, K. W., II, Cooper, S., Broxmeyer, H. (2003) Cell surface peptidase CD26/DPPIV mediates G-CSF mobilization of mouse progenitor cells Blood 101,4680-4686[Abstract/Free Full Text]
63 - Christopherson, K. W., II, Cooper, S., Hangoc, G., Broxmeyer, H. (2003) CD26 is essential for normal G-CSF-induced progenitor cell mobilization as determined by CD26–/– mice Exp. Hematol. 31,1126-1134[Medline]
64 - Epstein, R. (2004) The CXCL12-CXCR4 chemotactic pathway as a target of adjuvant breast cancer therapies Nat. Rev. Cancer 4,901-909[CrossRef][Medline]
65 - Pacheco, R., Martinez-Navio, J., Lejeune, M., Climent, N., Olivatt, H., Gatell, J., Gallart, T., Mallol, J., Lluis, C., Franco, R. (2005) CD26, adenosine deaminase, and adenosine receptors mediate costimulatory signals in the immunological synapse Proc. Natl. Acad. Sci. USA 102,9583-9588[Abstract/Free Full Text]
66 - Morimoto, C., Schlossman, S. (1998) The structure and function of CD26 in the T-cell immune response Immunol. Rev. 161,55-70[CrossRef][Medline]
67 - De Meester, I., Vanham, G., Kestens, L., Vanhoof, G., Bosmans, E., Gigase, P., Scharpe, S. (1994) Binding of adenosine deaminase to the lymphocyte surface via CD26 Eur. J. Immunol. 24,566-570[Medline]
68 - Dong, R., Kameoka, J., Hegen, M., Tanaka, T., Xu, Y., Schlossman, S., Morimoto, C. (1996) Characterization of adenosine deaminase binding to human CD26 on T cells and its biologic role in immune response J. Immunol. 156,1349-1355[Abstract]
69 - Gaspar, H., Bjorkegren, E., Parsley, K., Gilmour, K., King, D., Sinclair, J., Zhang, F., Giannakopoulos, A., Adams, S., Fairbanks, L. D., Gaspar, J., Henderson, L., Xu-Bayford, J. H., Davies, E., Veys, P., Kinnon, C., Thrasher, A. (2006) Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning Mol. Ther. 14,505-513[CrossRef][Medline]
70 - Sharoyan, S., Antonyan, A., Mardanyan, S., Lupidi, G., Cristalli, G. (2006) Influence of dipeptidyl peptidase IV on enzymatic properties of adenosine deaminase Acta Biochim. Pol. 53,539-546[Medline]
71 - Seguin-Devaux, C., Hanriot, D., Dailloux, M., Latger-Cannard, V., Zannad, F., Mertes, P., Longrois, D., Devaux, Y. (2005) Retinoic acid amplifies the host immune response to LPS through increased T lymphocytes number and LPS binding protein expression Mol. Cell. Endocrinol. 245,67-76[CrossRef][Medline]
72 - Iwata, M., Eshima, Y., Kagechika, H. (2003) Retinoic acids exert direct effects on T cells to suppress Th1 development and enhance Th2 development via retinoic acid receptors Int. Immunol. 15,1017-1025[Abstract/Free Full Text]
73 - Bauvois, B., Djavaheri-Mergny, M., Rouillard, D., Dumont, J., Wietzerbin, J. (2000) Regulation of CD26/DPPIV gene expression by interferons and retinoic acid in tumor B cells Oncogene 19,265-272[CrossRef][Medline]
74 - Irvine, A., Berney, J., Francis, G. (1990) Dissociation of the proliferation and differentiation stimuli of granulocyte colony-stimulating factor (G-CSF) Leukemia 4,203-209[Medline]
75 - Ballin, A., Lehman, D., Sirota, P., Litvinjuk, U., Meytes, D. (1998) Increased number of peripheral blood CD34+ cells in lithium-treated patients Br. J. Haematol. 100,219-221[CrossRef][Medline]
76 - Green, B., Irwin, N., Duffy, N., Gault, V., O'Harte, F. P., Flatt, P. R. (2006) Inhibition of dipeptidyl peptidase-IV activity by metformin enhances the antidiabetic effects of glucagon-like peptide-1 Eur. J. Pharmacol. 547,192-199[CrossRef][Medline]
77 - Lindsay, J., Duffy, N., McKillop, A., Ardill, J., O'Harte, F., Flatt, P., Bell, P. (2005) Inhibition of dipeptidyl peptidase IV activity by oral metformin in type 2 diabetes Diabet. Med. 22,654-657[CrossRef][Medline]
78 - Mest, H. (2006) Dipeptidyl peptidase-IV inhibitors can restore glucose homeostasis in type 2 diabetics via incretin enhancement Curr. Opin. Investig. Drugs 7,338-343[Medline]
79 - Miller, S., St Onge, E. (2006) Sitagliptin: a dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes Ann. Pharmacother. 40,1336-1343[Abstract/Free Full Text]
80 - Ahren, B. (2006) Vildagliptin: an inhibitor of dipeptidyl peptidase-4 with antidiabetic properties Expert Opin. Investig. Drugs 15,431-442[CrossRef][Medline]
81 - Nakamura, T., Uchiyama, S., Yamazaki, M., Iwata, M. (2006) Synergistic effect of cilostazol and dipyridamole mediated by adenosine on shear-induced platelet aggregation Thromb. Res. 119,511-516[CrossRef][Medline]
82 - Hofer, M., Pospisil, M., Weiterova, L., Znojil, V., Vacha, J., Hola, J., Vacek, A., Pipalova, I. (2001) Combination of drugs elevating extracellular adenosine with granulocyte colony-stimulating factor promotes granulopoietic recovery in the murine bone marrow after 5-fluorouracil treatment Physiol. Res. 50,521-524[Medline]
83 - Wang, T., Mentzer, R. J., Van Wylen, D. (1992) Interstitial adenosine with dipyridamole: effect of adenosine receptor blockade and adenosine deaminase Am. J. Physiol. 263,H552-H558[Medline]
84 - Hegedus, K., Keresztes, T., Fekete, I., Molnar, L. (1997) Effect of i.v. dipyridamole on cerebral blood flow, blood pressure, plasma adenosine and cAMP levels in rabbits J. Neurol. Sci. 148,153-161[CrossRef][Medline]
85 - Robak, T. (2001) Cladribine in the treatment of chronic lymphocytic leukemia Leuk. Lymphoma 40,551-564[Medline]
86 - Kay, N. (2006) Purine analogue-based chemotherapy regimens for patients with previously untreated B-chronic lymphocytic leukemia Semin. Hematol. 43,S50-S54[CrossRef][Medline]
87 - Gandhi, V., Plunkett, W. (2002) Cellular and clinical pharmacology of fludarabine Clin. Pharmacokinet. 41,93-103[CrossRef][Medline]
88 - Spiers, A. (1996) Deoxycoformycin (pentostatin): clinical pharmacology, role in the chemotherapy of cancer, and use in other diseases Haematologia (Budap.) 27,55-84[Medline]
89 - Riksen, N., Barrera, P., van den Broek, P., van Riel, P., Smits, P., Rongen, G. (2006) Methotrexate modulates the kinetics of adenosine in humans in vivo Ann. Rheum. Dis. 65,465-470[Abstract/Free Full Text]
90 - Jindra, P., Koza, V., Lysak, D., Vozobulova, V., Steinerova, K. (2005) Inefficiency of high-dose G-CSF alone as second mobilization regimen in fludarabin-cyclophosphamide-treated CLL patients who failed to mobilize after chemotherapy and G-CSF Bone Marrow Transplant. 35,729-730[CrossRef][Medline]
91 - Visani, G., Lemoli, R., Tosi, P., Martinelli, G., Testoni, N., Ricci, P., Piccaluga, P., Pastano, R., Liopardi, G., Dizdari, A., Motta, M., Rizzi, S., Tura, S. (1999) Fludarabine-containing regimens severely impair peripheral blood stem cells mobilization and collection in acute myeloid leukaemia patients Br. J. Haematol. 105,775-779[CrossRef][Medline]
92 - Tian, C., Bagley, J., Forman, D., Iacomini, J. (2006) Inhibition of CD26 peptidase activity significantly improves engraftment of retrovirally transduced hematopoietic progenitors Gene Ther. 13,652-658[CrossRef][Medline]
93 - Peranteau, W., Endo, M., Adibe, O. O., Merchant, A., Zoltick, P. W., Flake, A. W. (2006) CD26 inhibition enhances allogeneic donor cell homing and engraftment after in utero hematopoietic cell transplantation Blood 108,4268-4274[Abstract/Free Full Text]
94 - Korom, S., de Meester, I., Belyaev, A., Schmidbauer, G., Schwemmle, K. (2003) CD26/DPP IV in experimental and clinical organ transplantation Adv. Exp. Med. Biol. 524,133-143[Medline]
95 - Triplitt, C., Wright, A., Chiquette, E. (2006) Incretin mimetics and dipeptidyl peptidase-IV inhibitors: potential new therapies for type 2 diabetes mellitus Pharmacotherapy 26,360-374[CrossRef][Medline]
96 - Lenhard, J., Croom, D., Minnick, D. (2004) Reduced serum dipeptidyl peptidase-IV after metformin and pioglitazone treatments Biochem. Biophys. Res. Commun. 324,92-97[CrossRef][Medline]
97 - Baptista, T., Lacruz, A., de Mendoza, S., Guillen, M., Burguera, J. L., de Burguera, M., Hernández, L. (2000) Endocrine effects of lithium carbonate in healthy premenopausal women: relationship with body weight regulation Prog. Neuropsychopharmacol. Biol. Psychiatry 24,1-16[CrossRef][Medline]
98 - Hofer, M., Pospisil, M., Znojil, V., Vacek, A., Weiterova, L., Hola, J., Vacha, J. (2002) Drugs elevating extracellular adenosine promote regeneration of haematopoietic progenitor cells in severely myelosuppressed mice: their comparison and joint effects with the granulocyte colony-stimulating factor Eur. J. Haematol. 68,4-11[CrossRef][Medline]
99 - Hofer, M., Weiterova, L., Vacek, A., Znojil, V., Pospisil, M., Vacha, J. (2003) Elevation of extracellular adenosine mobilizes hematopoietic progenitor cells and granulocytes into peripheral blood and enhances the mobilizing effects of granulocyte colony-stimulating factor Eur. J. Haematol. 71,204-210[CrossRef][Medline]
100 - Rubocki, R., Parsa, J. R., Hershfield, M. S., Sanger, W., Pirruccello, S., Santisteban, I., Gordon, B., Strandjord, S., Warkentin, P. I., Coccia, P. F. (2001) Full hematopoietic engraftment after allogeneic bone marrow transplantation without cytoreduction in a child with severe combined immunodeficiency Blood 97,809-811[Abstract/Free Full Text]
101 - Carbonaro, D., Jin, X., Cotoi, D., Mi, T., Yu, X., Skelton, D., Dorey, F., Kellems, R., Blackburn, M., Kohn, D. (2008) Neonatal bone marrow transplantation of ADA-deficient SCID mice results in immunological reconstitution despite low levels of engraftment and an absence of selective donor T lymphoid expansion Blood Epub ahead of print
102 - Sekhsaria, S., Fleisher, T., Vowells, S., Brown, M., Miller, J., Gordon, I., Blaese, R., Dunbar, C., Leitman, S., Malech, H. (1996) Granulocyte colony-stimulating factor recruitment of CD34+ progenitors to peripheral blood: impaired mobilization in chronic granulomatous disease and adenosine deaminase-deficient severe combined immunodeficiency disease patients Blood 88,1104-1112[Abstract/Free Full Text]
103 - Campbell, T., Broxmeyer, H. (2008) CD26 inhibition and hematopoiesis: a novel approach to enhance transplantation Front. Biosci. 13,1795-1805[CrossRef][Medline]
104 - Focosi, D., Kast, R., Metelli, M., Benedetti, E., Galimberti, S., Papineschi, F., Petrini, M. (2008) Enhancement of hematopoietic stem cell engraftment by inhibition of CXCL12 proteolysis with sitagliptin, an oral dipeptidyl-peptidase IV inhibitor: a report in a case of delayed graft failure Leuk. Res. in press
105 - Chan, K., Grimley, M., Taylor, C., Wall, D. (2008) Early identification and management of graft failure after unrelated cord blood transplantation Bone Marrow Transplant. Epub ahead of print
106 - Zou, L., Barnett, B., Safah, H., Larussa, V., Evdemon-Hogan, M., Mottram, P., Wei, S., David, O., Curiel, T., Zou, W. (2004) Bone marrow is a reservoir for CD4+CD25+ regulatory T cells that traffic through CXCL12/CXCR4 signals Cancer Res. 64,8451-8455[Abstract/Free Full Text]
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ABSTRACT
INTRODUCTION
