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bioRxiv · 10.1101/2021.05.28.446246

Somatic mutation involving activated signaling, transcription, or tumor suppression is a premise of MDS evolving into AML

Li, X.·Chang, C.-K.·Xu, F.·Wu, L.-Y.·Guo, J.·He, Q.·Zhang, Z.
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Abstract

The transformation biology of secondary AML from MDS is still not fully understood. Here, we performed a large cohort of paired sequences including target, whole-exome and single cell sequencing to search AML transformation-related mutations (TRM). The results showed that fifty-five out of the 64 (85.9%) patients presented presumptive TRM involving activated signaling, transcription factors, or tumor suppressors. Most of TRM (63.6%, 35 cases) emerged at the leukemia transformation point. All five of the remaining nine patients analyzed by paired whole exome sequencing showed TRM which are not included in the reference targets. Single-cell sequencing indicated that the activated cell signaling route was related to TRM which take place prior to phenotypic development. Of note, defined TRM was limited to a small set of genes (less than ten, in the order: NRAS/KRAS, CEBPA, TP53, FLT3, RUNX1, CBL, PTPN11 and WT1, accounted for 91.0% of the mutations). In conclusion, somatic mutations involving in activated signaling, transcription factors, or tumor suppressors appeared to be a precondition for AML transformation from myelodysplastic syndromes. The TRM may be considered as new therapy targets.

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Li, X., Chang, C.-K., Xu, F., Wu, L.-Y., Guo, J., He, Q., Zhang, Z.. 2021-05-29. Somatic mutation involving activated signaling, transcription, or tumor suppression is a premise of MDS evolving into AML. https://doi.org/10.1101/2021.05.28.446246

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