Introduction:The myelodysplastic/myeloproliferative neoplasm (MDS/MPN) are a unique group of hematologic malignancies characterized by overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms. According to the 2016 WHO classification, the category includes atypical chronic myeloid leukemia (aCML), chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), MDS/MPN-unclassifiable (MDS/MPN-U), and refractory anemia with ring sideroblasts and thrombocytosis (RARS-T). The recent adaptation of next generation sequencing (NGS) in genetic testing increase our ability to use molecular approaches in the diagnosis and classification of MDS/MPN. This study aims to reveal the genetic mutation spectrum among different subgroups of Chinese MDS/MPN patients by a NGS-based targeted gene panel.

Method: We selected a cohort of 54 patients diagnosed with MDS/MPN collected from August, 2015 to April, 2017 in our department. Median age of 54 patients was 53 years (range, 1-85) and 72% were male. Thirty one (57.4%) patients with CMML, 10(18.5%) aCML, 7 (13%) JMML, and 6 (11.1%) with MDS/MPN-U were included in this cohort. Genomic DNA was extracted from the BM samples and then assayed on Ion Torrent platform with a panel of targeted sequencing of all exons of 52 genes focused myeloid neoplasms panel using NGS sequencing. The average depth was 1,000×. All sequencing data were analyzed using our in-house pipeline established on the basis of authoritative databases (1000 Genomes, PolyPhen, SIFT, COSMIC, etc).

Results: Of the 54 tested patients, we found in total 154 pathogenic variants (mean 2.85 variants per patient, rang 0-10), including 44 novel mutations (10 frameshift, 26 missense and 8 nonsense) , 53 patients exhibit at least one pathogenic mutation (98%), and 46(85%) had >1 mutation, 37 (69%) ≥3. Variants show allele frequencies ranging from 1.17% up to 100%. Mutations commonly found in our cohort included SETBP1 (35%) , TET2 (33%), NRAS (26%) , ASXL1 (22%), U2AF1 (17%), PTPN11 (13%), RUNX1 (13%), KRAS (11%), SRSF2 (11%), NF1(9%), RELN (9%), DNMT3A (7%), JAK2 (7%), CBL (7%), EZH2(7%), CEBPA (6%), FLT3 (6%), KIT (6%). However, the different MDS/MPN subgroups showed the different most frequently mutated genes: TET2, SETBP1, NRAS in CMML; SETBP1, TET2, U2AF1 in aCML; PTPN11, NRAS, ASXL1 in JMML; JAK2, and SETBP1, U2AF1 in MDS/MPN-U. In CMML, TET2 mutation seemingly showed mutually exclusive with SETBP1. In addition, compared with other genes, TET2, NRAS, DNMT3A were more likely to have a second mutation in the same patient ( see Figure1).

Conclusion: This study revealed the genetic mutation spectrum among different subgroups of MDS/MPN in Chinese patients, and the mutation profiling help us to increase the precision of diagnosis and classification.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.

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