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Title: Integrative genomic analysis of adult mixed phenotype acute leukemia delineates lineage associated molecular subtypes
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
Author's alias: 高折, 晃史
Issue Date: 10-Jul-2018
Publisher: Springer Nature
Journal title: Nature Communications
Volume: 9
Thesis number: 2670
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.
Rights: © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
URI: http://hdl.handle.net/2433/235742
DOI(Published Version): 10.1038/s41467-018-04924-z
PubMed ID: 29991687
Appears in Collections:Journal Articles

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