Impact of the International Consensus Classification of myelodysplastic syndromes.

The impact of the 2022 International Consensus Classification (ICC) of myelodysplastic syndromes (MDS) needs study. We analysed data from 989 MDS subjects classified using the 2016 World Health Organization (WHO) criteria to determine the impact of the new proposal. Our analyses suggested the ICC criteria of MDS-SF3B1 identifies a more homogenous disease entity than the WHO 2016 criteria of myelodysplastic syndromes with ring sideroblasts (MDS-RS). MDS, not otherwise specified with single lineage dysplasia (MDS, NOS-SLD) patients had a better prognosis than MDS, NOS with multilineage dysplasia (MDS, NOS-MLD) patients. MDS with mutated TP53 and MDS/acute myeloid leukaemia with mutated TP53 patients had the briefest survivals. These data support the ICC of MDS, which allows more accurate diagnoses and risk stratification.

IPSS-M has greater survival predictive accuracy compared with IPSS-R in persons ≥ 60 years with myelodysplastic syndromes.

There are considerable new data on mutation topography in persons with myelodysplastic syndromes (MDS). These data have been used to update conventional risk models such as the Revised International Prognostic Scoring System (IPSS-R). Whether the molecular IPSS (IPSS-M) which includes these data improves survival prediction accuracy is untested. To answer this question, we compared survival prediction accuracies of the IPSS-R and IPSS-M in 852 consecutive subjects with de novo MDS. Concordance statistics (C-statistics) of the IPSS-R and IPSS-M in the entire cohort were similar, 0.67 (95% Confidence Interval [CI] 0.64, 0.71) and 0.68 (0.64, 0.71). Average numbers of mutations and of IPSS-M related mutations were greater in persons ≥ 60 years (2.0 [Interquartile Range [IQR], 1, 3] vs. 1.6 [0, 2], P = 0.003; 1.6 [0, 2] vs. 1.3 [0, 2], P = 0.006). Subjects ≥ 60 years had a higher incidence of mutations in RUNX1, TP53, TET2, SRSF2, DNMT3A, STAG2, EZH2 and DDX41. In contrast, mutations in U2AF1 were more common in persons < 60 years. Next we tested survival prediction accuracy based on age < or ≥ 60 years. C-statistics of the IPSS-R and IPSS-M in subjects ≥ 60 years were 0.66 (0.61, 0.71) and 0.69 (0.64, 0.73) whereas in subjects < 60 years they were 0.67 (0.61, 0.72) and 0.65 (0.59, 0.71). These data indicate an advantage for the IPSS-M over the IPSS-R in subjects ≥ 60 years but not in those < 60 years probably because of a great frequency of mutations correlated with survival in those ≥ 60 years.

Comparison of the revised 4th (2016) and 5th (2022) editions of the World Health Organization classification of myelodysplastic neoplasms.

We used data from 852 consecutive subjects with myelodysplastic neoplasms (MDS) diagnosed according to the 2016 (revised 4th) World Health Organization (WHO) criteria to evaluate the 2022 (5th) edition WHO classification of MDS. 30 subjects previously classified as MDS with an NPM1 mutation were re-classified as acute myeloid leukaemia (AML). 9 subjects previously classified as MDS-U were re-classified to clonal cytopenia of undetermined significance (CCUS). The remaining 813 subjects were diagnosed as: MDS-5q (N = 11 [1%]), MDS-SF3B1 (N = 70 [9%]), MDS-biTP53 (N = 53 [7%]), MDS-LB (N = 293 [36%]), MDS-h (N = 80 [10%]), MDS-IB1 (N = 161 [20%]), MDS-IB2 (N = 103 [13%]) and MDS-f (N = 42 [5%]) and MDS-biTP53 (N = 53 [7%]). 34 of these subjects came from the 53 (64%) MDS-biTP53 previously diagnosed as MDS-EB. Median survival of subjects classified as MDS using the WHO 2022 criteria was 45 months (95% Confidence Interval [CI], 34, 56 months). Subjects re-classified as MDS-biTP53 and MDS-f had significantly briefer median survivals compared with other MDS sub-types (10 months, [8, 12 months] and 15 months [8, 23 months]). In conclusion, our analyses support the refinements made in the WHO 2022 proposal.

The association between BACH1 polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in a Chinese cohort.

OBJECTIVE: Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is related to hepatotoxic intermediaries, which are detoxified by glutathione S-transferases (GSTs). GSTM1 and GSTT1 are regulated by nuclear factor erythroid 2-related factor 2 (Nrf2) signalling pathway, and the BTB domain and CNC homologue 1 (Bach1) could compete with Nrf2 for binding to the DNA. Thus, bach1 may indirectly affect GSTs expression. The present study aimed to examine the role of tagSNPs in BACH1 in a Chinese population-based cohort. METHODS: A nested case-control study was conducted. Each ATDH case was matched with two controls by age, gender, treatment history, etc. Seven tagSNPs were detected and analysed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using a conditional logistic regression model. RESULTS: A total of 290 ATDH cases and 580 controls were included in the present study. Patients carrying GG genotype of rs372883 were at a lower risk of ATDH than with AA genotype (OR = 0.553, 95%CI: 0.357-0.857, P = .008), and significant differences were also found under recessive model (P = .021) and additive model (P = .009). Similar results were also found in the polymorphism of rs1153285 (AA vs. GG, OR = 0.574, 95%CI: 0.360-0.914, P = .019), and under its recessive model (P = .033) and additive model (P = .026). Two haplotypes of A-G-T and C-T-G were identified to be associated with ATDH development. Further subgroup analysis also suggested significant association between BACH1 polymorphisms and ATDH among certain and probable hepatotoxicity cases. CONCLUSIONS: This is the first study to explore the relationship between tagSNPs of BACH1 and ATDH in a Chinese cohort. Based on this cohort, genetic polymorphisms of BACH1 may be associated with susceptibility to ATDH in the Chinese population.