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Integrative genomic analysis of adult mixed phenotype acute leukemia delineates lineage associated molecular subtypes

Author

Listed:
  • Koichi Takahashi

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center
    Kyoto University)

  • Feng Wang

    (The University of Texas MD Anderson Cancer Center)

  • Kiyomi Morita

    (The University of Texas MD Anderson Cancer Center)

  • Yuanqing Yan

    (The University of Texas MD Anderson Cancer Center)

  • Peter Hu

    (The University of Texas MD Anderson Cancer Center)

  • Pei Zhao

    (The University of Texas MD Anderson Cancer Center)

  • Abdallah Abou Zhar

    (The University of Texas MD Anderson Cancer Center)

  • Chang Jiun Wu

    (The University of Texas MD Anderson Cancer Center)

  • Curtis Gumbs

    (The University of Texas MD Anderson Cancer Center)

  • Latasha Little

    (The University of Texas MD Anderson Cancer Center)

  • Samantha Tippen

    (The University of Texas MD Anderson Cancer Center)

  • Rebecca Thornton

    (The University of Texas MD Anderson Cancer Center)

  • Marcus Coyle

    (The University of Texas MD Anderson Cancer Center)

  • Marisela Mendoza

    (The University of Texas MD Anderson Cancer Center)

  • Erika Thompson

    (The University of Texas MD Anderson Cancer Center)

  • Jianhua Zhang

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Courtney D. DiNardo

    (The University of Texas MD Anderson Cancer Center)

  • Nitin Jain

    (The University of Texas MD Anderson Cancer Center)

  • Farhad Ravandi

    (The University of Texas MD Anderson Cancer Center)

  • Jorge E. Cortes

    (The University of Texas MD Anderson Cancer Center)

  • Guillermo Garcia-Manero

    (The University of Texas MD Anderson Cancer Center)

  • Steven Kornblau

    (The University of Texas MD Anderson Cancer Center)

  • Michael Andreeff

    (The University of Texas MD Anderson Cancer Center)

  • Elias Jabbour

    (The University of Texas MD Anderson Cancer Center)

  • Carlos Bueso-Ramos

    (The University of Texas MD Anderson Cancer Center)

  • Akifumi Takaori-Kondo

    (Kyoto University)

  • Marina Konopleva

    (The University of Texas MD Anderson Cancer Center)

  • Keyur Patel

    (The University of Texas MD Anderson Cancer Center)

  • Hagop Kantarjian

    (The University of Texas MD Anderson Cancer Center)

  • P. Andrew Futreal

    (The University of Texas MD Anderson Cancer Center)

Abstract

Mixed phenotype acute leukemia (MPAL) is a rare subtype of acute leukemia characterized by leukemic blasts presenting myeloid and lymphoid markers. Here we report data from integrated genomic analysis on 31 MPAL samples and compare molecular profiling with that from acute myeloid leukemia (AML), B cell acute lymphoblastic leukemia (B-ALL), and T cell acute lymphoblastic leukemia (T-ALL). Consistent with the mixed immunophenotype, both AML-type and ALL-type mutations are detected in MPAL. Myeloid-B and myeloid-T MPAL show distinct mutation and methylation signatures that are associated with differences in lineage-commitment gene expressions. Genome-wide methylation comparison among MPAL, AML, B-ALL, and T-ALL sub-classifies MPAL into AML-type and ALL-type MPAL, which is associated with better clinical response when lineage-matched therapy is given. These results elucidate the genetic and epigenetic heterogeneity of MPAL and its genetic distinction from AML, B-ALL, and T-ALL and further provide proof of concept for a molecularly guided precision therapy approach in MPAL.

Suggested Citation

  • Koichi Takahashi & Feng Wang & Kiyomi Morita & Yuanqing Yan & Peter Hu & Pei Zhao & Abdallah Abou Zhar & Chang Jiun Wu & Curtis Gumbs & Latasha Little & Samantha Tippen & Rebecca Thornton & Marcus Coy, 2018. "Integrative genomic analysis of adult mixed phenotype acute leukemia delineates lineage associated molecular subtypes," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04924-z
    DOI: 10.1038/s41467-018-04924-z
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    Cited by:

    1. Cheryl A. C. Peretz & Vanessa E. Kennedy & Anushka Walia & Cyrille L. Delley & Andrew Koh & Elaine Tran & Iain C. Clark & Corey E. Hayford & Chris D’Amato & Yi Xue & Kristina M. Fontanez & Aaron A. Ma, 2024. "Multiomic single cell sequencing identifies stemlike nature of mixed phenotype acute leukemia," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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