Impact of Concomitant Aberrant CD200 and BCL2 Overexpression on Outcome of Acute Myeloid Leukemia: A Cohort Study from a Single Center

Objective: CD200 and BCL2 overexpression is independently associated with inferior survival in acute myeloid leukemia (AML), and these two factors are frequently co-expressed; however, no data are available on the role of concomitant aberrant CD200 and BCL2 expression on outcome of AML patients. We aimed to elucidate the prognostic role of CD200/BCL2 co-expression and its association with specific leukemia subsets. Materials and Methods: We analyzed 242 adult AML patients uniformly treated with intensive chemotherapy, evaluating the impact of CD200 and BCL2 expression on complete remission (CR), disease-free survival, and overall survival (OS). Results: CD200 and BCL2 were expressed in 139 (57.4%) and 137 (56.6%) cases, respectively, with 92 patients (38%) displaying double positivity (DP), 58 (24%) displaying double negativity (DN), and 92 patients expressing only either CD200 (n=47) or BCL2 (n=45). CR was achieved in 71% of cases, being less frequent in DP patients (60%) compared to other groups (76%-81%, p<0.001). In the whole population 3-year OS was 44%, being lower in DP patients (28%) than in patients with single CD200 or BCL2 expression (47%) or DN cases (60%; p=0.004). Other factors associated with worse OS were advanced age, CD34 positivity, secondary AML, and high white blood cell count at diagnosis; combining these 4 factors with CD200/BCL2 DP, we identified 6 groups with significantly different rates of survival (3-year OS ranging from 90% to 0%). Conclusion: Our data support a synergistic effect of CD200 and BCL2 in AML cells, conferring an enhanced survival capacity in a permissive microenvironment and resulting in worse prognosis.