High co-expression of Cd135 and Cd117 predicts poor outcome in acute myeloid leukemia: A prospective study

Abstract

Background: The significance of the mutations in FLT3 and c-kit genes in AML has been well established but the role of their expression is not studied together. The aim of this study was to evaluate clinical significance of FLT3 (CD135) and c-kit (CD117) co-expression on myeloblasts in AML. Methods: Five ml peripheral blood/bone marrow from consecutive AML patients at diagnosis from April 2008 to May 2010 was evaluated by flow-cytometry. CD135 and CD117 expression was evaluated on dim CD45 positive myeloblasts. Positive expression was considered as >20% surface antigen expression. Results: During the study period, there were 115 AML patients with median age 16 years and male:female ratio 2.02:1. M2 was the most common subtype 57% (66/115) followed by M4 14% (16/115). Cytogenetically (n = 85) these patients were classified as good risk in 20 (23%), intermediate risk in 50 (59%) and poor risk in 15 (18%) patients. Flt3 internal tandem duplication was present in 20 (17%) patients. CD135 was positive in 95 (82%) patients; CD117 was positive in 104 (90%) patients; co-expression of CD135 and CD117 was observed in 74 (64%) patients. In those patients who co-expressed CD135 and CD117, the median expression was 34.1% of the gated myeloblasts and patients were classified as high co-expression (>/= 34.1% expression) and low (<34.1% expression or no co-expression). High co-expression did not statistically correlate with FLT3 internal tandem duplication (p = 0.432) and cytogenetics (p = 0.244). Out of 115 patients, 86 (75%) achieved remission. At a median follow-up of 18.7 months, EFS and OS was 28% and 37% respectively for the entire cohort. Patients with high co-expression of CD135 and CD117 in comparison to those with low co-expression had significantly inferior EFS (19% vs 34% p = 0.0002) and OS (26% vs 44% p = 0.0003). In step wise Cox regression multivariate analysis the hazard ratio for high hemoglobin, WBC count and co-expression of CD135 and CD117 was 0.63, 1.73 and 2.44 respectively. Conclusion: High co-expression of proliferative markers CD135 and CD117 is an independent prognostic factor for poor outcome in AML.