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

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 Coyle, Marisela Mendoza, Erika Thompson, Jianhua Zhang, Courtney D. DiNardo, Nitin Jain, Farhad Ravandi, Jorge E. Cortes, Guillermo Garcia-Manero, Steven Kornblau, Michael Andreeff, Elias Jabbour, Carlos Bueso-Ramos, Akifumi Takaori-Kondo, Marina Konopleva, Keyur Patel, Hagop Kantarjian and P. Andrew Futreal
Additional contact information
Koichi Takahashi: The University of Texas MD Anderson Cancer Center
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
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

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04924-z

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