PROGNOSTIC IMPACT OF CD244 EXPRESSION IN PATIENTS WITH ACUTE LEUKEMIA

Abstract

Background: Acute leukemia is a heterogeneous clonal hematological malignancy. Despite advances in diagnosis, prognosis, risk stratification, and treatment, cure rate remains modest, and relapse-related mortality remains high. CD244 has been implicated in the maintenance of stemness of leukemia initiating cells, but not in hematopoietic stem cells, suggesting its potential as a novel therapeutic target against leukemia initiating cells for cure of acute leukemia (AL). Methods: This prospective longitudinal study included assessment of CD244 expression using multiparameter flow cytometry in 141 newly diagnosed acute leukemia patients (85 AML and 56 ALL) and sixteen age and sex matched controls. Bone marrow samples were analyzed at diagnosis, after induction in patients achieved complete remission and at relapse at any point of time. Associations between CD244 expression and clinicopathological characteristics, treatment response, and survival outcomes were investigated. Results: CD244 expression was significantly elevated in acute leukemia patients, with noticeably higher expression and MFI in AML compared to both ALL and controls (both P<0.001). Although CD244 expression was also elevated in ALL compared to controls (P=0.030), suggesting CD244 can serve as a lineage discriminator differentiating between both types of leukemia. Also, in both AML and ALL patients, CD244 expression and MFI were significantly elevated at diagnosis and relapse compared to remission. These dynamic changes in CD244 can help in monitoring disease progression. Furthermore, higher CD244 expression was associated with adverse risk stratification and poorer clinical outcomes in AML and ALL.  Cox regression analysis revealed that elevated CD244 MFI was independent predictor of inferior overall survival (OS) (adjusted HR=1.322, 95% CI: 1.154–2.673, P=0.037) together with non complete remission (adjusted HR=11.690, P<0.001) and relapse (adjusted HR=3.962, P=0.010). However, in ALL higher CD244 MFI was associated with shorter disease-free survival (DFS) in univariate analysis (HR=5.364, 95% CI: 1.034–27.832, P=0.046). Conclusion: CD244 represents promising differentiating biomarker in acute leukemia. Its dynamic changes throughout the disease course and its association with adverse clinicopathological features support its potential role in disease monitoring and highlight its potential as therapeutic target.