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Published online before print August 17, 2007

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0207095

Received for publication February 6, 2007.
Revised July 12, 2007.
Accepted for publication July 13, 2007.

Brief Communication

The association of ICAM-1 Exon 6 (E469K) but not of ICAM-1 Exon 4 (G241R) and PECAM-1 Exon 3 (L125V) polymorphisms with the development of differentiation syndrome in acute promyelocytic leukemia

Adriana I. Dore ^*, Barbara A. A. Santana-Lemos ^*, Virginia M. Coser , Flávia L. S. Santos ^*, Leandro F. Dalmazzo ^*, Ana S. G. Lima ^*, Rafael H. Jacomo ^*, Jorge Elias Jr., Roberto Passetto Falcão ^*, Waldir V. Pereira , and Eduardo M. Rego ^*@

*Hematology and Imaging Divisions, Department of Internal Medicine, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil; and Federal University of Santa Maria, Santa Maria, RS, Brazil

^@ To whom correspondence should be addressed. E-mail: emrego{at}hcrp.fmrp.usp.br.

	Abstract

The use of all trans-retinoic acid (ATRA) is the basis of treatment of acute promyelocytic leukemia (APL) and represents the paradigm of differentiation therapy. In general, ATRA is well-tolerated but may be associated with a potentially lethal side-effect, referred to as retinoic acid or differentiation syndrome (DS). The cellular and molecular mechanisms of DS are poorly understood and involve changes in the adhesive qualities and cytokine secretion of leukemic cells during ATRA-induced differentiation. As leukocyte extravasation is a key event in DS pathogenesis, we analyzed the association between the polymorphisms at Exon 4 (G241R) and Exon 6 (E469K) of ICAM-1 and Exon 3 (L125V) of PECAM-1 genes with DS development in APL patients treated with ATRA and anthracyclines. DS was diagnosed in 23/127 (18.1%) APL patients at an average of 11.5 days after the start of ATRA. All patients presented respiratory distress associated with increased ground-glass opacity in chest radiographies. Other accompanying symptoms were: fever not attributable to infection (65.2%), generalized edema (37.5%), weight gain (37.5%), and impairment of renal function (8.6%). We detected an association between development of DS and the AA genotype at Codon 469 of ICAM-1 (odds ratio of 3.5; 95% confidence interval: 1.2–10.2). Conversely, no significant association was detected between G241R or L125V polymorphisms at Exon 4 of ICAM-1 and Exon 3 of PECAM-1, respectively. Our results suggest that susceptibility to DS in APL patients may be influenced by genetic variation in adhesion molecule loci.

Key Words: acute myelogenous leukemia • all trans-retinoic acid • adhesion molecules