The Transcripts of Platelet-Endothelial Adhesion Molecules and Inflamatory Chemokine Activation Pathway Molecules Are Hyperexpressed in the Bone Marrow of Acute Promyelocytic Leukemia Patients Presenting Severe Coagulopathy

Although Acute Promyelocytic Leukemia (APL) is now considered one of the most curable forms of acute leukemia, it is an aggressive disease associated with a high frequency of bleeding and thrombosis. Indeed, the leading cause of treatment failure in APL is not disease resistance or recurrence but death in induction by hemorrhage caused by APL-associated coagulopathy in which blast-derived pro-coagulant and fibrinolytic factors (Annexin A2 and Tissue factor), as well as cytokines, microparticles and proteases were reported to participate of the pathogenesis. However, why some APL patients are more prone to develop bleeding diathesis than others is presently unknown. In order to address this issue, we performed microarray analysis of leukemic cells from 6 pairs of patients matched for age, sex, and WBC and platelet counts at diagnosis, but differed regarding the presence of clinical signs of APL-associated coagulopathy and fibrinogen levels (Table 1). All patients were enrolled in the IC-APL trial whose results have been reported {Blood;121(11):1935-43}.Table 1Clinical characteristics of the selected patients at the diagnosis of APL. Values represent the median and percentiles (25 – 75)Fibrinogen(mg/dL)Age(years)WBC(x109/L)Platelets(x109/L)nClinical signs of CoagulopathyYESGroup 164 (51.5-98.5)41.5 (26.6-55.2)15.9 (7.8-29.9)31 (19-41.1)6NOGroup 2236 (194-431)40.8 (29.8-60.9)17.3 (4.7-28.9)23(4.2-70.5)6