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Background  Recently, various blood cell lineages expressing the  BCR-ABL  fusion gene in Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) have been reported. However, the biological and clinical significance of these  BCR-ABL  lineages has not been established; therefore, we aimed to clarify the impacts of these different  BCR-ABL -expressing lineages.    Patients  Multi-lineage  BCR-ABL  expression (multi-Ph) was defined as  BCR-ABL  expression outside of the B-lineage compartment, as determined by fluorescence  in situ  hybridization (FISH) in peripheral blood neutrophils and bone marrow clots, and flow cytometry-sorted polymerase chain reaction (PCR). We analyzed  IKZF1  deletion patterns by PCR, examined gene expression profiles using RNA sequencing, and compared treatment outcomes across different  BCR-ABL -expressing lineages.    Results  Among the 21 multi-Ph patients in our 59-patient cohort (36%),  BCR-ABL  expression was detected at the multipotential progenitor level. However, no  IKZF1  deletion patterns or gene expression profiles were identified that were specific for multi-Ph. However, multi-Ph patients were found to have better survival rates than patients with uni-lineage  BCR-ABL  expression [event-free survival (EFS): 74 vs. 33%,  P  = 0.01; overall survival (OS): 79 vs. 44% at 4 years,  P  = 0.01]. In multivariate analyses, multi-Ph was identified as a good prognostic factor for both EFS and OS.    Conclusion  We confirmed that more than one-third of Ph+ALL patients could be classified as mutli-Ph. Although no specific molecular characteristics were identified for multi-Ph, this phenotype was associated with better treatment outcomes.

frontiers in oncology

Multi-Lineage BCR-ABL Expression in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Is Associated With Improved Prognosis but No Specific Molecular Features