beta2 Integrins are characteristically absent in acute promyelocytic leukemia and rapidly upregulated in vivo upon differentiation with all-trans retinoic acid.
Although little is known about migration of hematopoietic stem cells and their neoplastic counterparts into tissues and peripheral blood, adhesion proteins likely play an important role. We studied 339 patients with acute myelogenous leukemia (AML) to discern the relationship between adhesion protein expression, circulating blasts, and white blood cell (WBC) count. Expression levels of CD11b and CD11c strongly correlated with increased WBC count, independent of FAB subtype (p<0.0001). However, 93% (25/27) of cases of AML-M3 completely lacked beta2 integrin expression, compared to 11% (35/312) of the non-M3 cases (p<0.0001). Seven of the 27 patients with AML-M3 were followed during standard induction therapy with ATRA. Within 3 days, weak CD11c became detectable, followed by CD11b and CD11a. Our data suggest an important link between beta2 integrin expression and the level of circulating leukemic cells in AML. We demonstrate the clinical usefulness of a panel of beta2 integrins (CD11a, CD11b and CD11c) in accurate prediction of AML-M3, and recommend inclusion of this immunophenotypic analysis to identify patients who require ATRA therapy. Finally, we illustrate the rapidity at which AML-M3 blasts up-regulate beta2 integrins, and suggest a possible association between this finding and the tissue infiltration that characterizes the "ATRA syndrome".
Wu
Jamie J
JJ
Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine, Tampa, FL, United States.
Cantor
Alan
A
Moscinski
Lynn C
LC
D000704:Analysis of Variance; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000097:blood / Q000235:genetics; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000473:pathology; D018821:CD18 Antigens / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007621:Karyotyping; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D007958:Leukocyte Count; D011237:Predictive Value of Tests; D012008:Recurrence; D012189:Retrospective Studies; D014212:Tretinoin / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000970:Antineoplastic Agents; D018821:CD18 Antigens; D014212:Tretinoin