Genomic Analysis Reveals Molecular Features of Mixed Phenotype Acute Leukemia Subtypes

NEW YORK (GenomeWeb) – Researchers from St. Jude Children’s Research Hospital, the University of North Carolina at Chapel Hill, and other centers around the world have characterized molecular features in a high-risk leukemia subtype called mixed phenotype acute leukemia (MPAL).

The team used exome sequencing, RNA sequencing, whole-genome sequencing, and/or SNP arrays to profile tumor samples from more than 100 children with MPAL — a disease marked by both myeloid and lymphoid leukemia features. The results, which appeared online today in Nature, revealed molecular differences between T/myeloid and B/myeloid subtypes of MPAL. In particular, the T/myeloid form often contained alterations affecting both copies of the WTI gene, while the B/myeloid MPAL more often harbored ZNF384 rearrangements.

“The findings suggest the ZNF384 rearrangement defines a distinct leukemia subtype and the alteration should be used to guide treatment,” co-corresponding author Charles Mullighan, a pathology researcher at St. Jude and co-leader of the center’s hematological malignancies program, said in a statement.

More broadly, the researchers’ analyses suggested that the mixed features found in the MPAL tumors reflect genetic mutations that originally occurred in hematopoietic progenitor cells, which went on to differentiate into varied blood cell types.

As many as 3 percent of childhood

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