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BCR-ABL1 -like B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains poorly characterized in adults. We sought to establish the frequency and outcome of adolescent and adult  BCR-ABL1 -like ALL using a novel RNA-Seq signature in a series of patients with BCP-ALL. To this end, we developed and tested an RNA-Seq custom panel of 42 genes related to a  BCR-ABL1 -like signature in a cohort of 100 patients with BCP-ALL and treated with risk-adapted ALL trials. Mutations related to  BCR-ABL1 -like ALL were studied in a panel of 33 genes by next-generation sequencing (NGS). Also,  CRLF2  overexpression and  IKZF1 / CDKN2A/B  deletions were analyzed. Twenty out of 79 patients (12–84 years) were classified as  BCR-ABL1 -like (25%) based on heatmap clustering, with significant overexpression of  ENAM ,  IGJ , and  CRLF2  ( P  ≤ 0.001). The  BCR-ABL1 -like subgroup accounted for 29% of 15–60-year-old patients, with the following molecular characteristics:  CRLF2  overexpression (75% of cases),  IKZF1  deletions (64%),  CDKN2A/B  deletions (57%), and  JAK2  mutations (57%). Among patients with postinduction negative minimal residual disease, those with the  BCR-ABL1 -like ALL signature had a higher rate of relapse and lower complete response duration than non- BCR-ABL1 -like patients ( P  = 0.007). Thus, we have identified a new molecular signature of  BCR-ABL1 -like ALL that correlates with adverse prognosis in adult patients with ALL.

A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics