A limited low-cost method to identify subgroup of B cell-Acute Lymphoblastic Lukemia (B-ALL) with overexpressed CRLF2, JAK2, ABL1 - results from a prospective study.

Background: Ph-like ALL is a subtype of ALL with profile similar to Philadelphia-positive ALL but without BCR::ABL1 gene fusion and shows adverse clinical profile and inferior outcomes. This study aimed to identify Ph-like ALL using a simplified and cost-effective workflow in adolescent and young adult (AYA) instead of standardized ideal gene expression profiling. Due to the use of limited panel, the subgroup of B-ALL has been named as "B-ALL with overexpressed CRLF2, JAK2, ABL1". Methods: We recruited AYA (13-40 years) patients with B-ALL. Patients were identified as "B-ALL with overexpressed CRLF2, JAK2, ABL1" if they had overexpression of any one of Cytokine receptor-like factor-2 (CRLF2) by flow cytometry (FCM), ABL1, or JAK2 by Reverse transcription polymerase chain reaction (RT-PCR). Results: Of 100 patients, N = 14 (14%) were classified as Ph + ve (or BCR::ABL1 fusion present). Remaining N = 86 (86%) were classified into three groups: N = 41 (41%) Ph-ve, N = 29 (29%) "B-ALL with overexpressed CRLF2, JAK2, ABL1", and N = 16 (16%) unclassified (JAK2 and ABL1 negative, and CRLF2 expression unknown). During induction, 18/100 patients died, and 82 had end-therapy bone marrow studies with MRD data in 65 cases. CR was achieved in 75/100 (75%) cases. The CR was significantly lower (72%, p = 0.01) and MRD positivity was significantly higher (40%, p = 0.02) in "B-ALL with overexpressed CRLF2, JAK2, ABL1" than in other groups. For entire population, median follow up was 26 months, median EFS was 15.1 months and median OS was 15.9 months. For "B-ALL with overexpressed CRLF2, JAK2, ABL1", median EFS (1.5 months, p < 0.001) and median OS (5.1 months, p = 0.001) were significantly lower than the other three groups. Conclusion: Using 3 markers representing "B-ALL with overexpressed CRLF2, JAK2, ABL1", we identified a group with poor outcomes. Conventional identification of Ph-like is expensive, requires expertise, and is difficult to implement in practice. Hence, this minimalistic approach may be further validated in future studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-025-01968-2.