High methylation of the 4-aminobutyrate aminotransferase gene predicts a poor prognosis in patients with myelodysplastic syndrome

To evaluate the clinical significance of N-ras mutations in the myelodysplastic syndrome (MDS) archival bone marrow samples from 252 patients were studied for the presence of N-ras exon I mutations using polymerase chain reaction amplification and differential oligonucleotide hybridization. Subsequently, clinical information about these patients was obtained and analyzed. Of 220 evaluable patients, 20 (9%) had point mutation of N-ras involving codon 12. Individuals with N- ras mutation had a significantly shorter survival period than those who were N-ras negative (P = .02). An increased risk of acute myelogenous leukemia (AML) was also found in patients with N-ras mutations (P = .005). N-ras mutations were not associated with any French-American- British (FAB) subtype, with the presence of increased myeloblasts, or with chromosomal aberrations in the bone marrow. However, the presence of increased bone marrow blasts was strongly associated with poor survival rate and risk of AML (P < .001 for each). After stratifying for the percentage of blasts, N-ras mutations remained significantly associated with shorter survival period (P = .04) and increased risk of AML (P = .02). Bone marrow cytogenetic abnormalities, particularly when multiple abnormalities were present, were significantly associated with a poor prognosis (P < .001). In conclusion, N-ras mutation, although relatively infrequent in MDS, is associated with short survival period and increased probability of developing AML.

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Differential U2AF1 mutation sites, burden and co-mutation genes can predict prognosis in patients with myelodysplastic syndrome

Scientific Reports ◽

10.1038/s41598-020-74744-z ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Haiqiong Wang ◽

Yongbo Guo ◽

Zhenkun Dong ◽

Tao Li ◽

Xinsheng Xie ◽

...

Keyword(s):

Survival Rate ◽

Myelodysplastic Syndrome ◽

Gene Mutation ◽

Poor Prognosis ◽

Gene Mutations ◽

Chromosome 8 ◽

Common Mutation ◽

Mutation Load ◽

Mutation Site ◽

Increased Risk

Abstract To investigate the U2AF1 gene mutation site, mutation load and co-mutations genes in patients with myelodysplastic syndrome (MDS) and their effects on prognosis. Gene mutation detection by next-generation sequence and related clinical data of 234 MDS patients were retrospectively collected and analyzed for the relationship between the clinical characteristics, treatment efficacy and prognosis of U2AF1 gene mutation. Among the 234 MDS patients, the U2AF1 gene mutation rate was 21.7% (51 cases), and the median variant allele frequency was 39.5%. Compared with the wild type, the U2AF1 mutant had a higher incidence of chromosome 8 aberration, and was positively correlated with the occurrence of ASXL1, RUNX1, SETBP1 gene mutation, negatively correlated with SF3B1, NPM1 genes mutation (p < 0.05). The most common mutation site of U2AF1 was S34F (32 cases), while U2AF1 Q157P site mutations had a higher incidence of chromosome 7 abnormalities (p = 0.003). The U2AF1 gene mutation more frequently coincided with signal pathway related gene mutations (p = 0.043) with a trend of shortened overall survival. Among patients with U2AF1 gene mutations, those with ASXL1 mutations were prone to develop into acute myeloid leukemia, those with RUNX1 mutations had an increased risk of relapse, and those with TET2 mutations had higher 1-year survival rate. Compared with the patient group of lower mutation load (VAF ≤ 40%), the group with higher mutation load of U2AF1 (VAF > 40%) had a significantly lower 1-year survival rate (46.1% and 80.5%, p = 0.027). The criteria of U2AF1 VAF > 40% is an independent indicator for poor prognosis of MDS patients. VAF > 40% of U2AF1 is an independent factor of short OS in MDS patients. MDS patients with a mutation in the Q157P site of U2AF1 and a higher U2AF1 mutation load suggests poor prognosis, and co-mutated genes in U2AF1 can affect disease progression and prognosis.

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Cytogenetic Abnormalities Predict Disease Progression in Primary Myelodysplastic Syndrome: A Multicentric Study in 508 Chinese Patients.

Blood ◽

10.1182/blood.v104.11.1451.1451 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1451-1451

Author(s):

Bing Chen ◽

Wei-Li Zhao ◽

Jie Jin ◽

Yong-Quan Xue ◽

Xin Cheng ◽

...

Keyword(s):

Myelodysplastic Syndrome ◽

Poor Prognosis ◽

Mononuclear Cells ◽

Chinese Patients ◽

Structural Abnormality ◽

Multicentric Study ◽

Cytogenetic Abnormalities ◽

Chromosome Translocations ◽

Cytogenetic Aberrations ◽

Cell Disorder

Abstract Myelodysplastic syndrome (MDS) is a clonal stem cell disorder characterized by ineffective hematopoiesis and frequent leukemia progression. Cytogenetic abnormalities are presented in MDS patients and predict poor prognosis. To better define their relevance to clinical outcome in Chinese patients with primary MDS, cytogenetic analysis was performed in 508 cases and retrospectively compared with clinical data. The median age was 49 years which was 10 years younger than that of western patients. The median overall survival was 34 (range 1–161) months, with the 2-year and 5-year survival rate of 50.0% and 15.0%, respectively. Among 367 cases with evaluable karyotype in bone marrow mononuclear cells, cytogenetic abnormalities were found in 136 of them (37.1%), including 56 cases (15.3%) of numeric abnormality and 80 cases (21.8%) of structural abnormality. Higher incidence of cytogenetic abnormality was found in RAEB-T (43/86, 50.0%) and RAEB (44/106, 41.5%) patients than that of RA patients (38/143, 26.6%). RAEB and RAEB-T had more cases of non-hypodipoidy, double aberrations with translocation, and complex aberrations. In RA, the most frequent aberrations were duplication and numeric changes. This study also showed RAEB appears to be the course of MDS that genome turbulence was under the evolution pressure. In RAEB-T, the genome abnormalities tend to be uniform and behaved as special translocation, which is in accordance with the clinical behavior of AL. Poor prognosis and early leukemia transformation were observed in the patients with cytogenetic abnormalities, especially with complex cytogenetic aberrations and chromosome translocations. In conclusion, cytogenetic abnormalities possess strong predictive value on disease outcome in primary MDS patients.

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