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Introduction: The prognosis of acute lymphoblastic leukemia (ALL) in adolescents and adults is poor, and recurrence is an important cause of their death. Changes of genetic information play a vital role in the pathogenesis and recurrence of ALL; however, the impact of molecular genetic mutations on disease diagnosis and prognosis remains unexplored. This study aimed to explore the frequency spectrum of gene mutations and their prognostic significance, along with the minimal residual disease (MRD) level and hematopoietic stem cell transplantation (HSCT), in adolescent and adult patients aged ≥15 years with ALL. Methods: The basic characteristics, cytogenetics, molecular genetics, MRD level, treatment regimen, and survival outcome of patients with untreated ALL (≥15 years) were collected, and the correlation and survival analysis were performed using the SPSS 25.0 and R software. Results: This study included 404 patients, of which 147 were selected for next-generation sequencing (NGS). NGS results revealed that 91.2% of the patients had at least one mutation, and 67.35% had multiple (≥2) mutations. NOTCH1, PHF6, RUNX1, PTEN, JAK3, TET2, and JAK1 were the most common mutations in T-ALL, whereas FAT1, TET2, NARS, KMT2D, FLT3, and RELN were the most common mutations in B-ALL. Correlation analysis revealed the mutation patterns, which were significantly different between T-ALL and B-ALL. In the prognostic analysis of 107 patients with B-ALL, multivariate analysis showed that the number of mutations ≥5 was an independent risk factor for overall survival and the RELN mutation was an independent poor prognostic factor for event-free survival. Discussion: The distribution of gene mutations and the co-occurrence and repulsion of mutant genes in patients with ALL were closely related to the immunophenotype of the patients. The number of mutations ≥5 and the RELN mutation were significantly associated with poor prognosis in adolescent and adult patients with ALL. [ABSTRACT FROM AUTHOR]

Background: Genomic sequencing technologies have identified isocitrate dehydrogenase ( IDH ) mutations in haematological malignancies. The prognostic implications of somatic IDH mutation ( mIDH ) in myelodysplastic syndromes (MDS) remain controversial. Methods: Mutations in IDH1 and IDH2 were detected using genomic sequencing technologies in 97 patients with MDS. Results: Seven (7.2%) mutations were identified: 3 in IDH1 (all R132C) and 4 in IDH2 (3 R140Q and 1 R140L). The frequency of mutation was 16.6% (2/12) in refractory anaemia with excess blasts (RAEB)-1 and 14.7% (5/34) in RAEB-2. IDH1 / 2 mutations were closely associated with higher bone marrow blast counts (median 10.0 vs. 2.3%; p = 0.019) and lower absolute neutrophil counts (median 0.44 x 10 9 /L vs. 1.21 x 10 9 /L; p = 0.027). All IDH mutations were mutually exclusive and heterozygous. IDH mutations were not significantly correlated with any specific karyotype. Patients with IDH1 mutations exhibited shorter overall and progression-free survival (OS and PFS; p = 0.039 and p = 0.042, respectively), whereas IDH2 mutations did not affect OS or PFS ( p = 0.560 and p = 0.218, respectively). Multivariate analysis indicated that IDH1 mutation ( p = 0.018; hazard ratio [HR] 4.735; 95% confidence interval [CI] 1.299-17.264), karyotype risk ( p = 0.036; HR 1.619; 95% CI 1.033-2.539) and the revised International Prognostic Scoring System risk category ( p < 0.0001; HR 2.122; 95% CI 1.401-3.213) were independent inferior prognostic factors. Conclusions: IDH1 mutation is associated with a poor prognosis. [ABSTRACT FROM AUTHOR]