Mixed Phenotype Acute Leukemia (MPAL) Exhibits Frequent Mutations in DNMT3A and Activated Signaling Genes

Abstract 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 an...

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Bibliographic Details
Published in:Experimental hematology 2016-08, Vol.44 (8), p.740-744
Main Authors: Eckstein, Olive S., MD, Wang, Linghua, MD, PhD, Punia, Jyotinder N., M.D, Kornblau, Steven M., MD, Andreeff, Michael, MD, PhD, Wheeler, David A., PhD, Goodell, Margaret A., PhD, Rau, Rachel E., MD
Format: Article
Language:English
Subjects:
Adolescent
Adult
Advanced Basic Science
Clonal Evolution - genetics
Cluster Analysis
DNA (Cytosine-5-)-Methyltransferases - genetics
DNA Methyltransferase 3A
Epigenesis, Genetic
Exome
Gene Expression Profiling
Gene Expression Regulation, Leukemic
Hematology, Oncology and Palliative Medicine
High-Throughput Nucleotide Sequencing
Humans
Leukemia, Biphenotypic, Acute - genetics
Leukemia, Biphenotypic, Acute - metabolism
Middle Aged
Mutation
Signal Transduction
Young Adult
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Summary:Abstract 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. 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 we identified provides potential biological insights and is likely to have clinical relevance for patients with this poor-prognosis disease.
ISSN:0301-472X
1873-2399
DOI:10.1016/j.exphem.2016.05.003