Cytogenetics ; Humans ; Myelodysplastic Syndromes ; genetics

Humans ; Mutation ; Myelodysplastic Syndromes/genetics*

The myelodysplastic syndrome (MDS) is an abnormal clonal proliferation disease resulting from disorder of hematopoietic stem cells/progenitor cells and is characterized by ineffective hematopoiesis and high risk of transforming into acute leukemia. The present experimental studies in gene, chromosome, cytokines and biochemical aspects may put the genetically models for clarifying the pathogenesis of MDS, help to early evaluation of disease prognosis and eventually develop the strategies of more effective prevention and treatment methods for MDS. In this article, the advances of chromosome, gene, cytokines and biochemical aspects in pathogenesis of MDS are summarized on basis of proceedings of ASH meeting in 2007 years.
Humans ; Myelodysplastic Syndromes ; genetics ; metabolism ; pathology

Epigenesis, Genetic ; Humans ; Myelodysplastic Syndromes ; genetics ; therapy

Epigenesis, Genetic ; Humans ; Myelodysplastic Syndromes ; genetics

MicroRNA (miRNA), evolutionarily conserved, endogenous, small, noncoding RNA molecule of about 22 nucleotides in length, have been recently attributed a crucial role in numerous physiological and pathological processes including the regulation of cellular development, differentiation, proliferation, apoptosis and oncogenesis. Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematologic disorders characterized clinically and morphologically by ineffective hematopoiesis and increased risk of leukaemic transformation. The role of miRNA abnormal expression in pathogenesis and prognosis of MDS is reviewed in this article, including miRNA related with pathogenesis, miRNA related with prognosis of MDS and so on.
Hematopoiesis ; Humans ; MicroRNAs ; Myelodysplastic Syndromes ; genetics ; pathology

Animals ; Humans ; Myelodysplastic Syndromes ; diagnosis ; genetics ; therapy

OBJECTIVETo investigate NPM1 gene mutations in patients with primary myelodysplastic syndromes (MDS) and the clinical characteristics of patients with NPM1 mutants.

METHODSGenomic DNA corresponding to exon 12 of NPM1 gene was amplified by polymerase chain reaction (PCR) in 232 patients with primary MDS. Identification of mutants was by direct sequencing and classification of mutation types by sequencing followed by plasmid cloning.

RESULTSNPM1 mutants were found in 9 patients (3.9%). All the mutants were type A. As compared with those with NPM1 wild type, patients with the mutant were of lower ANC \[0.60 (0.12 - 2.91) × 10(9)/L vs 1.02 (0 - 10.23) × 10(9)/L, P = 0.046\], higher blast percent in bone marrow \[0.050 (0 - 0.090) vs 0.025 (0 - 0.190), P = 0.035\], decreased BFU-E \[0 (0 - 0)/10(5) BMMNC vs 6 (0 - 40)/10(5) BMMNC, P = 0.038\] and increased serum vitamin B(12) \[936.40 (373.80 - 2400.00) pmol/L vs 557.85 (17.00 - 3032.10) pmol/L, P = 0.045\] The chromosomal karyotypes of patients with NPM1 mutant were predominantly normal.

CONCLUSIONMDS patients with NPM1 gene mutations have some unique clinical and laboratory features. The results give new hint for the pathogenesis of MDS development and progression.

Humans ; Mutation ; Myelodysplastic Syndromes/genetics* ; Prognosis ; Splicing Factor U2AF/genetics*

OBJECTIVE: To investigate the clinical significance of the targeted next-generation sequencing assay for patients with suspected myeloid malignancies. METHODS: A total of 39 hematopenia patients with suspected myeloid malignamies in Department of Hematology of The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University from January 2018 to April 2019 were treated, 20 hot spot genes of myelodysplastic syndrome (MDS) were detected. RESULTS: Regarding the diagnostic type, there were 7 cases of idiopathic cytopenia of undetermined significance (ICUS), 8 cases of clonal cytopenias of undetermined significance (CCUS) and 24 cases of myeloid myeloid malignancies which included 18 cases of MDS, 4 cases of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and 2 cases of acute myeloid leukemia. Positive mutation was detected in 70.8% (17/24) of myeloid malignancy patients , and 72.7% (16/22) in MDS and MDS/MPN patients. The main mutation types were ASXL1, TET2 and RUNX1. Compared with gene negative group, there were no significant differences in sex, age (＜60 years old or ≥60 years old), proportion of bone marrow blast cells (＜5% or≥5%) and cytogenetics (good, medium and poor) (P＞0.05). Furthermore, all 8 CCUS patients showed positive mutation, and the incidence of double or multiple mutation in CCUS group was significantly lower than that of the MDS and MDS/MPN group (37.5% vs 54.5%) (P=0.002). The mutation types between the two groups were similar, and there was no significant difference in variant allele frequency (P＞0.05). CONCLUSION Our results suggest that there are high rates of double or multiple mutations in myeloid malignancies, especially in patients with MDS and MDS/MPN. Targeted sequencing assay can improve the diagnosis of myeloid malignancies, and guide clinical treatment.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Mutation ; Myelodysplastic Syndromes/genetics* ; Myelodysplastic-Myeloproliferative Diseases ; Patients