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

Xiaoli Mi, Gabriel Griffin, Winston Lee, Sanjay Patel, Robert Ohgami, Chi Young Ok, Sa Wang, Julia T. Geyer, Wenbin Xiao, Mikhail Roshal, Jacqueline S. Garcia, Lewis B. Silverman, Stephen E. Sallan, Jon C. Aster, Marian H. Harris, Olga K. Weinberg

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1358-1367
Number of pages10
JournalAmerican Journal of Hematology
Issue number11
StatePublished - Nov 2018
Externally publishedYes

ASJC Scopus subject areas

  • Hematology


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