TY - JOUR
T1 - Integrative genomic analysis of adult mixed phenotype acute leukemia delineates lineage associated molecular subtypes
AU - Takahashi, Koichi
AU - Wang, Feng
AU - Morita, Kiyomi
AU - Yan, Yuanqing
AU - Hu, Peter
AU - Zhao, Pei
AU - Zhar, Abdallah Abou
AU - Wu, Chang Jiun
AU - Gumbs, Curtis
AU - Little, Latasha
AU - Tippen, Samantha
AU - Thornton, Rebecca
AU - Coyle, Marcus
AU - Mendoza, Marisela
AU - Thompson, Erika
AU - Zhang, Jianhua
AU - Dinardo, Courtney D.
AU - Jain, Nitin
AU - Ravandi, Farhad
AU - Cortes, Jorge E.
AU - Garcia-Manero, Guillermo
AU - Kornblau, Steven
AU - Andreeff, Michael
AU - Jabbour, Elias
AU - Bueso-Ramos, Carlos
AU - Takaori-Kondo, Akifumi
AU - Konopleva, Marina
AU - Patel, Keyur
AU - Kantarjian, Hagop
AU - Futreal, P. Andrew
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-018-04924-z
DO - 10.1038/s41467-018-04924-z
M3 - Article
C2 - 29991687
AN - SCOPUS:85049863343
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2670
ER -