CD117 as a Lineage-Associated Biomarker in Acute Leukemia: A Favorable Prognostic Marker in AML and an Adverse Predictor in ALL

Acute leukemia comprises heterogeneous hematologic malignancies. CD117 (c-KIT), encoded by the KIT proto-oncogene, is a receptor tyrosine kinase involved in hematopoietic cell survival, proliferation, and differentiation. CD117 expression was assessed in 118 acute myeloid leukemia (AML) and 106 acute lymphoblastic leukemia (ALL) cases and correlated with clinical, immunophenotypic, molecular, and survival parameters. CD117 was expressed in 82.2% of AML and 17.9% of ALL cases. In AML, CD117 positivity was associated with AML-M2 (p < 0.001), core-binding factor (CBF) abnormalities (p = 0.010), and favorable European LeukemiaNet (ELN) 2022 risk (p = 0.041). CD117 independently predicted improved overall survival (OS) in CBF-adjusted (aHR = 0.450, 95% CI: 0.219–0.924, p = 0.030) and ELN-adjusted models (aHR = 0.295, 95% CI: 0.127–0.684, p = 0.004). CD117 was associated with improved event-free survival (EFS) only in the ELN-adjusted model (aHR = 0.374, 95% CI: 0.159–0.882, p = 0.025). In ALL, CD117 was associated with T-cell lineage (p < 0.001) and independently predicted inferior OS (aHR = 4.171, 95% CI: 1.375–12.656, p = 0.012) and EFS (aHR = 3.145, 95% CI: 1.153–8.576, p = 0.025). In T-ALL, it predicted poorer OS (aHR = 3.316, 95% CI: 1.043–10.537, p = 0.042). In conclusion, CD117 has disease-specific prognostic significance, predicting favorable outcomes in AML but adverse outcomes in ALL, particularly T-ALL.