TY - JOUR
T1 - Mixed-phenotype acute leukemia (MPAL) exhibits frequent mutations in DNMT3A and activated signaling genes
AU - Eckstein, Olive S.
AU - Wang, Linghua
AU - Punia, Jyotinder N.
AU - Kornblau, Steven M.
AU - Andreeff, Michael
AU - Wheeler, David A.
AU - Goodell, Margaret A.
AU - Rau, Rachel E.
N1 - Publisher Copyright:
© 2016 ISEH - International Society for Experimental Hematology
PY - 2016/8/1
Y1 - 2016/8/1
N2 - Mixed-phenotype acute leukemia (MPAL) is a heterogeneous group of poor-prognosis leukemias with immunophenotypic features of at least two cell lineages. The full spectrum of genetic mutations in this rare disease has not been elucidated, limiting our understanding of disease pathogenesis and our ability to devise targeted therapeutic strategies. Here, we sought to define the mutational landscape of MPAL by performing whole-exome sequencing on samples from 23 adult and pediatric MPAL patients. We identified frequent mutations of epigenetic modifiers, most notably mutations of DNMT3A, in 33% of adult MPAL patients. Mutations of activated signaling pathways, tumor suppressors, and transcription factors were also frequent. Importantly, many of the identified mutations are potentially therapeutically targetable, with agents currently available or in various stages of clinical development. Therefore, the mutational spectrum that we have identified provides potential biological insights and is likely to have clinical relevance for patients with this poor-prognosis disease.
AB - Mixed-phenotype acute leukemia (MPAL) is a heterogeneous group of poor-prognosis leukemias with immunophenotypic features of at least two cell lineages. The full spectrum of genetic mutations in this rare disease has not been elucidated, limiting our understanding of disease pathogenesis and our ability to devise targeted therapeutic strategies. Here, we sought to define the mutational landscape of MPAL by performing whole-exome sequencing on samples from 23 adult and pediatric MPAL patients. We identified frequent mutations of epigenetic modifiers, most notably mutations of DNMT3A, in 33% of adult MPAL patients. Mutations of activated signaling pathways, tumor suppressors, and transcription factors were also frequent. Importantly, many of the identified mutations are potentially therapeutically targetable, with agents currently available or in various stages of clinical development. Therefore, the mutational spectrum that we have identified provides potential biological insights and is likely to have clinical relevance for patients with this poor-prognosis disease.
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U2 - 10.1016/j.exphem.2016.05.003
DO - 10.1016/j.exphem.2016.05.003
M3 - Article
C2 - 27208809
AN - SCOPUS:84989825250
SN - 0301-472X
VL - 44
SP - 740
EP - 744
JO - Experimental Hematology
JF - Experimental Hematology
IS - 8
ER -