Screening of mutations in the additional sex combs like 1, transcriptional regulator, tumor protein p53, and KRAS proto-oncogene, GTPase/NRAS proto-oncogene, GTPase genes of patients with myelodysplastic syndrome

Abstract

Abstract. Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal bone marrow disorders characterized by ineffective hematopoiesis, different degrees of cellular dysplasia, and increased risk of progression to acute myeloid leukemia. International Prognostic Scoring System is the gold standard for MDS classification; however, patients exhibiting different clinical behaviors often coexist in the same group, indicating that the currently available scoring systems are insufficient. The genes that have recently been identified as mutated in MDS, including additional sex combs like 1, transcriptional regulator (ASXL1), tumor protein p53 (TP53), and KRAS proto-oncogene and GTPase (KRAS)/NRAS proto-oncogene, GTPase (NRAS), may contribute to a more comprehensive classification, as well as to the prognosis and progression of the disease. In the present study, the mutations in the ASXL1, TP53 and NRAS/KRAS genes in 50 patients were evaluated by sequencing genomic bone marrow DNA. Nine patients (18%) presented with at least one type of mutation. Mutations in TP53 were the most frequent in six patients (12%), followed by ASXL1 in two patients (4%) and NRAS in one patient (2%). The nine mutations were detected in patients with low-and high-risk MDS. The screening of mutations in MDS cases contributes to the application of personalized medicine.

Screening and identification of key candidate genes and pathways in myelodysplastic syndrome by bioinformatic analysis

“…Aberrant EZH2 splicing and/or EZH2 mutations which impaired histone H3 lysine 27 tri-methylation may be associated with the pathogenesis of MDS (Shirahata-Adachi et al, 2017). NRAS was thought to be significantly associated with MDS, especially in the progression to leukemia (Leite et al, 2017; Makishima, 2019). RUNX1 mutation was observed in approximately 10% of patients with MDS.…”