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

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 c...

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Published in:Nature communications 2018-07, Vol.9 (1), p.2670-12, Article 2670
Main Authors: Takahashi, Koichi, Wang, Feng, Morita, Kiyomi, Yan, Yuanqing, Hu, Peter, Zhao, Pei, Zhar, Abdallah Abou, Wu, Chang Jiun, Gumbs, Curtis, Little, Latasha, Tippen, Samantha, Thornton, Rebecca, Coyle, Marcus, Mendoza, Marisela, Thompson, Erika, Zhang, Jianhua, DiNardo, Courtney D., Jain, Nitin, Ravandi, Farhad, Cortes, Jorge E., Garcia-Manero, Guillermo, Kornblau, Steven, Andreeff, Michael, Jabbour, Elias, Bueso-Ramos, Carlos, Takaori-Kondo, Akifumi, Konopleva, Marina, Patel, Keyur, Kantarjian, Hagop, Futreal, P. Andrew
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Language:English
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Summary: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. Mixed phenotype acute leukemia (MPAL) is a rare leukemia that presents both myeloid and lymphoid markers on blasts. Here the authors perform genomic analysis to show MPAL involves genetic and epigenetic heterogeneity and is genetically distinct from AML, B-ALL, and T-ALL.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-018-04924-z