A new study is suggesting that 3 specific genetic alterations may help identify pediatric patients with acute megakaryoblastic leukemia (AMKL) at high risk who may benefit from allogeneic stem cell transplants. The study, which has been published in Nature Genetics, is the largest to date and used next-generation sequencing technology to define the genetic missteps that drive AMKL in children without Down syndrome.1

The standard recommendation by many pediatric oncologists is treatment with allogeneic stem cell transplantation during a patient’s first remission. In the current study, the researchers identified several genetic alterations that are important predictors of treatment success. The alterations include the fusion genes CBFA2T3-GLIS2, KMT2A, and NUP98-KDM5A, which are all associated with reduced survival compared to other pediatric AMKL subtypes.

AMKL is rare in adults, but accounts for about 10% of pediatric acute myeloid leukemia (AML). Along with the sequencing data, researchers analyzed patients’ gene expression and long-term survival. The results showed that non-Down syndrome pediatric AMKL can be divided into 7 subgroups based on the underlying genetic alteration, pattern of gene expression, and treatment outcome.

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Investigators also identified cooperating mutations that help to fuel AMKL in different subgroups. The cooperating mutations include changes in the RB1 gene and recurring mutations in the RAS and JAK pathways. These pathways have been reported in other cancers.


1. de Rooij JD, Branstetter C, Ma J, et al. Pediatric non-Down syndrome acute megakaryoblastic leukemia is characterized by distinct genomic subsets with varying outcomes. Nat Genet. 2017 Jan 23. doi: 10.1038/ng.3772 [Epub ahead of print]