Journal of Leukocyte Biology eBioscience full spectrum cell analysis
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published online as doi:10.1189/jlb.0607348 on September 25, 2007

Published online before print September 25, 2007
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jlb.0607348v1
83/1/173    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sun, Q.
Right arrow Articles by Chan, L. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sun, Q.
Right arrow Articles by Chan, L. C.
(Journal of Leukocyte Biology. 2008;83:173-180.)
© 2008 by Society for Leukocyte Biology

Aberrant dendritic cell differentiation initiated by the Mll-Een fusion gene does not require leukemic transformation

Q. Sun*, C. T. Kong*,{dagger}, F. P. Huang* and L. C. Chan*,1

* Departments of Pathology, S. H. Ho Foundation Research Laboratories, and
{dagger} Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

1 Correspondence: Department of Pathology, Division of Hematology, The University of Hong Kong, University Pathology Building, Queen Mary Hospital, 102 Pokfulam Road, Pokfulam, Hong Kong, SAR, China. E-mail: chanlc{at}pathology.hku.hk

Dendritic cells (DCs), as specialized APCs, play a key role in the induction of anti-tumor immunity. They originate from bone marrow (BM) progenitors, which are frequently the targets of chromosomal translocations leading to development of leukemia. Aberrant DC differentiation and functions have been observed and are widely reported in patients with leukemia. It is not clear, however, whether such defects are a direct effect of a leukemic fusion gene or simply an outcome of the clinical disease. In this study, we demonstrate for the first time that knockin of the Mll-Een fusion gene can affect myeloid DC differentiation and functions directly, independent of the leukemic disease activities. We showed that the Mll-Een-expressing BM cells [enhanced green fluorescent protein+ (EGFP+)] from leukemic and nonleukemic mice had similarly impaired DC differentiation capacities with functional abnormalities. In contrast, BM cells without Mll-Een expression (EGFP–) showed normal DC differentiation and functions. A reduction in the frequency of CD11c+ DCs was also observed within the EGFP+ population in spleen and lymph nodes, and these cells were dysfunctional. Taken together, our findings suggest that the Mll-Een fusion gene can affect myeloid DC differentiation directly and functions in a cell-autonomous manner, where fully leukemic transformation of the hematopoietic progenitors is not required exclusively. Therefore, the study provides evidence for a direct causal relationship between leukemic gene fusion and abnormal DC differentiation, possibly contributing to the development of leukemia.

Key Words: myeloid leukemia • development






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 by the Society for Leukocyte Biology.