Landscape of genetic alterations of myeloid neoplasms in 305 Chinese cases

Objective To analyze the landscape of genetic alterations of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). Methods Second-generation sequencing for common mutant genes was performed in the bone marrow cells derived from 305 myeloid leukemia patients (including 186 cases of AML, 64 cases of MDS, 27 cases of MPN, and 28 cases of MDS/MPN) treated in our hospital from January 2017 to January 2019. The gene mutation map was drawn. The mutation ratios of the genes and gene pathways of each myeloid tumor and the mutation rate of each mutant gene were compared among the different myeloid neoplasms. Results There were 606 mutations detected among 30 genes in the 305 cases. There were 15.4% cases with 0 mutation and 58.0% with more than 1 mutation. And up to 7 mutations were found in 1 case. Mutations of TET2, DNMT3A, NRAS, CEBPA, JAK2, C-KIT, U2AF1, and NPM1 were most common in the myeloid neoplasms. Mutations of signaling pathway-related genes accounted for over 50% in AML, MPN and MDS/MPN, and less than 10% in MDS. Mutations of transcription factors-related genes covered over 50% in AML, and less than 5% in MPN. Mutations of epigenetics-related gene were over 50% in all myeloid neoplasms. RNA splicing factors were mutated for over 30% in MDS and MDS/MPN, and less than 5% in AML. Mutations in signaling pathway-related genes such as NRAS and C-KIT were more prone to low mutation rates, and those of epigenetics-related genes such as TET2 and DNMT3A were more prone to high mutation rates. Conclusion The genetic landscapes are different among AML, MDS, MPN, and MDS/MPN. The mutation ratios of signaling pathway-related genes are quite low in MDS, so are the ratios of transcription factors-related genes in MPN. Meanwhile, the ratios of RNA splicing factors- and epigenetics-related genes are quite high in MDS and MDS/MPN, respectively