Abstract: Background: A Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk B-cell ALL subtype that is identified by a gene expression profile similar to Philadelphia chromosome-positive ALL, and lacking the BCR-ABL1 fusion. In this study, we analyzed molecular and clinical data to examine the coexistence and prognostic implications of CRLF2 overexpression and JAK2 r683 mutations in adult Ph-like ALL; we evaluate the potential utility of these biomarkers for risk stratification. Methods: In this study, we enrolled newly diagnosed fifty adult Ph-like ALL patients. Fluorescence In Situ Hybridization (FISH) was employed to evaluate CRLF2 expression, and Sanger sequencing was employed to identify JAK2 mutations. Results: The mean age of the 50 patients was 38.86 years, with a range of 18 to 64 years. Typically, 70% of the patients were male. Concerning CRLF2, only nine patients (18%) had expressed CRLF2 and all showed wild type JAK2 r6839 expression. CRLF2 demonstrated a significant connection with cytogenetic risk (p < 0.003). Moreover, CRLF2 manifested significant connection with relapse-free survival (RFS) and overall survival (OS), with positive CRLF2 correlating with reduced RFS and diminished OS, Positive CRLF2 significantly increase hazard of mortality by 7.54 folds while it significantly increases hazard of relapse by 6 folds.