Genomic and clinical characterization of B/T mixed phenotype acute leukemia reveals recurrent features and T-ALL like mutations.

TitleGenomic and clinical characterization of B/T mixed phenotype acute leukemia reveals recurrent features and T-ALL like mutations.
Publication TypeJournal Article
Year of Publication2018
AuthorsMi X, Griffin G, Lee W, Patel S, Ohgami R, Ok CYoung, Wang S, Geyer JT, Xiao W, Roshal M, Garcia JS, Silverman LB, Sallan SE, Aster JC, Harris MH, Weinberg OK
JournalAm J Hematol
Volume93
Issue11
Pagination1358-1367
Date Published2018 11
ISSN1096-8652
KeywordsAdolescent, Adult, Drug Therapy, Female, Genomics, Hematopoietic Stem Cell Transplantation, High-Throughput Nucleotide Sequencing, Humans, Immunophenotyping, Leukemia, Biphenotypic, Acute, Male, Middle Aged, Mutation, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Young Adult
Abstract

The B/T subtype of mixed phenotype acute leukemia (B/T MPAL) is defined by co-expression of antigens of both B- and T-cell lineages on leukemic blasts. Although it has been suggested that multilineage antigen expression portends poor response to chemotherapy, the clinical characteristics and driver mutations that underlie the pathogenesis of this rare subtype of acute leukemia are scarcely known. We identified nine cases of B/T MPAL from multiple institutions and correlated clinical and immunophenotypic findings with next-generation sequencing data. We report that B/T MPAL commonly presents with lymphadenopathy in adolescence and young adulthood. While the tumors have diverse cytogenetic and genomic perturbations, recurrent acquired aberrations include mutations in the putative transcriptional regulator PHF6 and the JAK-STAT and Ras signaling pathways. Alterations were also identified in genes encoding hematopoietic transcription factors, cell cycle regulators/tumor suppressors, and chromatin modifying enzymes. The genomic landscape of B/T MPAL strongly resembles that of T-ALL subgroups associated with early developmental arrest, while genetic alterations that are common in B-ALL were rarely seen. Two-thirds of the patients responded to ALL-based chemotherapy with or without stem cell transplantation. Our observations lay the groundwork for further study of the unique biology and clinical trajectory of B/T MPAL.

DOI10.1002/ajh.25256
Alternate JournalAm J Hematol
PubMed ID30117174
PubMed Central IDPMC8193761
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
Related Faculty: 
Julia Geyer, M.D. Sanjay Patel, M.D., MPH

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