Context.—: In the 2016 update of the World Health Organization (WHO) classification of hematopoietic neoplasms, BCR-ABL1-like B-acute lymphoblastic leukemia/lymphoma (B-ALL) is added as a new provisional entity that lacks the BCR-ABL1 translocation but shows a pattern of gene expression very similar to that seen in B-ALL with BCR-ABL1.
Objective.—: To review the kinase-activating alterations and the diagnostic approach for BCR-ABL1-like B-ALL.
Data sources.—: We provide a comprehensive review of BCR-ABL1-like B-ALL based on recent literature and the 2016 update of the World Health Organization classification of hematopoietic neoplasms.
Conclusions.—: Several types of kinase-activating alterations (fusions or mutations) are identified in BCR-ABL1-like B-ALL. The main categories are alterations in the ABL class family of genes, encompassing ABL1, ABL2, PDGFRB, PDGFRA (rare), and colony-stimulating factor 1 receptor (CSF1R) fusions, or the JAK2 class family of genes, encompassing alterations in JAK2, CRLF2, EPOR, and other genes in this pathway. These alterations determine the sensitivity to tyrosine kinase inhibitors. As a wide variety of genomic alterations are included in this category, the diagnosis of BCR-ABL1-like B-ALL is extremely complex. Stepwise algorithms and comprehensive unbiased testing are the 2 ways to approach the diagnosis of BCR-ABL1-like B-ALL.