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. CortesGuillermo Garcia-Manero, Steven Kornblau, Michael Andreeff, Elias Jabbour, Carlos Bueso-Ramos, Akifumi Takaori-Kondo, Marina Konopleva, Keyur Patel, Hagop Kantarjian, P. Andrew Futreal

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Article number2670
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Takahashi, K., Wang, F., Morita, K., Yan, Y., Hu, P., Zhao, P., Zhar, A. A., Wu, C. J., Gumbs, C., Little, L., Tippen, S., Thornton, R., Coyle, M., Mendoza, M., Thompson, E., Zhang, J., Dinardo, C. D., Jain, N., Ravandi, F., ... Futreal, P. A. (2018). Integrative genomic analysis of adult mixed phenotype acute leukemia delineates lineage associated molecular subtypes. Nature communications, 9(1), [2670]. https://doi.org/10.1038/s41467-018-04924-z