Additional Mutations Identified in Relapse-Specific AML

Friday, January 13, 2012 (Last Updated: 01/16/2012)

FRIDAY, Jan. 13 (HealthDay News) -- Relapse of acute myeloid leukemia (AML) is associated with acquisition of new mutations and clonal evolution, according to a letter published online Jan. 11 in Nature.

Li Ding, Ph.D., from Washington University in St. Louis, and colleagues sequenced the primary tumor and relapse genomes of eight patients with AML to identify the mutational spectrum associated with relapse. Somatic mutations were verified using deep sequencing.

The researchers discovered two clonal evolution patterns during relapse: either the founding clone from the primary tumor gained mutations and evolved into a relapse clone, or a subclone of the founding clone survived treatment, gained mutations, and then expanded. In all cases, the founding clone was not eradicated by chemotherapy. In all eight cases, comparison of the relapse-specific versus primary tumor mutations showed an increase in transversions.

"Taken together, these data demonstrate that AML cells routinely acquire a small number of additional mutations at relapse, and suggest that some of these mutations may contribute to clonal selection and chemotherapy resistance. The AML genome in an individual patient is clearly a 'moving target'; eradication of the founding clone and all of its subclones will be required to achieve cures," the authors write.


Specialties Hematology & Oncology

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