Features and impacts on the prognosis of gene mutations in patients with acute myeloid leukemia

Wu, Ming; Guo, Ziwen; Huang, Guan‐Jiang; Ye, Yong-Bin

doi:10.4149/neo_2021_201230n1426

Cited by 6 publications

(2 citation statements)

References 13 publications

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“…Genetic abnormality has important impact on AML prognosis, not only the well-known NCCN risk stratification involved cytogenetic abnormity and molecule genes, but also other recent identified prognostic genes [25][26][27]. Therefore, we then detected the gene mutations in our patients and found 49 mutated genes which were classified as first-, second-, and third-class mutations.…”

Section: Discussionmentioning

confidence: 95%

Venetoclax plus azacitidine and donor lymphocyte infusion in treating acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation

Zhao

et al. 2021

Ann Hematol

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This study aimed to evaluate the efficacy and safety of venetoclax plus azacitidine and donor lymphocyte infusion (DLI) in treating patients with relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Twenty-six AML patients who relapsed after allo-HSCT were enrolled and treated with venetoclax plus azacitidine and DLI. Complete remission with incomplete recovery (CRi), partial remission (PR), and objective remission rate (ORR) were assessed, and then event-free survival (EFS) and overall survival (OS) were evaluated. Besides, adverse events were documented. Additionally, whole exome sequencing was performed in bone marrow samples. The CRi, PR, and ORR rates were 26.9%, 34.6%, and 61.5%, respectively. The median time of EFS and OS was 120 (95% CI: 71–610) days and 284.5 (95% CI: 81–610) days, respectively. The most common adverse events were hematologic system adverse events including agranulocytosis, anemia, and thrombocytopenia, while the adverse events of other systems were relatively less and milder. In addition, no serious adverse events existed. Of note, there were 6 (23.1%) patients who developed GVHD. As for gene mutation, 49 mutated genes were found, which were categorized as first-, second-, and third-class mutations, and then further analysis revealed that the first-class mutations were not correlated with EFS or OS. Additionally, the most frequent mutated genes were FLT3, CEBPA, DNMT3A, KIT, KRAS, and NRAS. Venetoclax plus azacitidine and DLI is efficient and tolerant in treating patients with relapsed AML after allo-HSCT, implying this combined therapy as a potential treatment option in the studied patients.

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Section: Discussionmentioning

confidence: 95%

Venetoclax plus azacitidine and donor lymphocyte infusion in treating acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation

Zhao

et al. 2021

Ann Hematol

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“…After excluding duplicated records, we screened the results based on title and abstract and selected 179 studies for further full-text evaluation. Finally, 32 studies [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ] were included in our meta-analysis. Figure 1 shows the flowchart of study selection.…”

Section: Resultsmentioning

confidence: 99%

The Prognostic Value of TP53 Mutations in Adult Acute Myeloid Leukemia: A Meta-Analysis

Qin

Han²

2022

Transfus Med Hemother

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Objective: Mutations of the tumor protein p53 (TP53) gene were considered to be associated with an unfavorable prognosis in acute myeloid leukemia (AML). This meta-analysis aimed to systematically elucidate the prognostic value of TP53 mutation in adult patients with AML. Method: A comprehensive literature search was conducted for eligible studies published before August 2021. The primary endpoint was overall survival (OS). Pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were calculated for prognostic parameters. Subgroup analyses based on intensive treatment were performed. Results: Thirty-two studies with 7,062 patients were included. As compared to wild-type carriers, AML patients with TP53 mutations had significantly shorter OS (HR: 2.40, 95% CI: 2.16–2.67, I2: 46.6%). Similar results were found in DFS (HR: 2.87, 95% CI: 1.88–4.38), EFS (HR: 2.56, 95% CI: 1.97–3.31), and RFS (HR: 2.40, 95% CI: 1.79–3.22). Mutant TP53 predicted inferior OS (HR: 2.77, 95% CI: 2.41–3.18) in the intensively treated AML subgroup, compared with the non-intensively treated group (HR: 1.89, 95% CI: 1.58–2.26). Among intensively-treated AML patients, the age of 65 did not affect the prognostic value of TP53 mutations. Besides, TP53 mutation was also strongly associated with an elevated risk of adverse cytogenetics, which conferred a dismal OS in AML patients (HR: 2.03, 95% CI: 1.74–2.37). Conclusion: TP53 mutation exhibits a promising potential for discriminating AML patients with a worse prognosis, thus being capable of serving as a novel tool for prognostication and therapeutic decision-making in the management of AML.

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Clinical and prognostic profile of SRSF2 and related spliceosome mutations in patients with acute myeloid leukemia

et al. 2023

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BackgroundMutations in splicing factor (SF) genes are frequently detected in myelodysplastic syndrome, but rare data about the clinical and prognostic relevance of these mutations in acute myeloid leukemia (AML) have been reported. MethodsA total of 368 newly diagnosed non-M3 AML patients were included in this study. Next generation sequencing including four SF genes was performed on the genomic DNA. The clinical features and survival were analyzed using statistical analysis. SRSF2 P95H function was assessed by CCK8 assay. ResultsWe found that 64 of 368 patients harbored SF mutations. The SF mutations were much more frequent in older or male patients compared with SF-wild patients. SRSF2 mutations were shown obviously coexisted with IDH2 mutation. The level of measurable residual disease after the rst chemotherapy was higher in SF-mutated patients compared to that in SF-wild patients, while the complete remission rate was signi cantly decreased. And the overall survival (OS) of SF-mutated patients was shorter than that of SF-wild patients. Moreover, our multivariable analysis suggests that the index of male, Kit mutation or ZRSR2 mutation was the independent risk factor for OS. SRSF2 mut was associated with older age, higher proportion of peripheral blasts or abnormal cell proportion by FCM (Flow CytoMetry). Functionally, the mutation of SRSF2 P95H signi cantly promoted the proliferation of AML cells. ConclusionSpliceosome mutation is a distinct subgroup of AML frequently associated with clinic-biological features and poor outcome. SRSF2 mut could be potential targets for novel treatment in AML.

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Features and impacts on the prognosis of gene mutations in patients with acute myeloid leukemia

Cited by 6 publications

References 13 publications

Venetoclax plus azacitidine and donor lymphocyte infusion in treating acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation

Venetoclax plus azacitidine and donor lymphocyte infusion in treating acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation

The Prognostic Value of TP53 Mutations in Adult Acute Myeloid Leukemia: A Meta-Analysis

Clinical and prognostic profile of SRSF2 and related spliceosome mutations in patients with acute myeloid leukemia

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