4.0 Article

Comprehensive Mutation Profile in Acute Myeloid Leukemia Patients with RUNX1-RUNX1T1 or CBFB-MYH11 Fusions

Journal

TURKISH JOURNAL OF HEMATOLOGY
Volume 39, Issue 2, Pages 84-93

Publisher

GALENOS YAYINCILIK
DOI: 10.4274/tjh.galenos.2022.2021.0641

Keywords

Core-binding factor; Acute myeloid leukemia; Mutation; Next-generation sequencing

Categories

Funding

  1. Young Scientists Foundation of Changzhou No. 2 People's Hospital [2019K002]
  2. Science and Technology Project of the Changzhou Health Committee [QN202035]
  3. Science and Technology Development Fund Project of Nanjing Medical University [NMUB201]
  4. Major Science Project of the Changzhou Health Commission [ZD202018]
  5. Project of Science and Technology Support for Social Development of the Science and Technology Bureau of Changzhou [CE20205027]
  6. Changzhou Sci-Tech Program [CJ20210068]

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This study retrospectively analyzed the gene mutations in 134 patients with CBF-AML. The most common mutations were found in c-KIT and NRAS, while mutations related to epigenetic modification were less frequent. Patients with different chromosomal translocations exhibited different mutation profiles, and the frequencies of mutations in signaling pathways and cohesin varied among different chromosomal translocation types. AML patients with chromosomal translocations had significantly higher white blood cell counts if they had c-KIT or NRAS mutations.
Objective: This study was undertaken with the aim of better understanding the genomic landscape of core-binding factor (CBF) acute myeloid leukemia (AML). Materials and Methods: We retrospectively analyzed 112 genes that were detected using next-generation sequencing in 134 patients with de novo CBF-AML. FLT3-ITD, NPM1, and CEBPA mutations were detected by DNA-PCR and Sanger sequencing. Results: In the whole cohort, the most commonly mutated genes were c-KIT (33.6%) and NRAS (33.6%), followed by FLT3 (18.7%), KRAS (13.4%), RELN (8.2%), and NOTCH1 (8.2%). The frequencies of mutated genes associated with epigenetic modification, such as IDH1, IDH2, DNMT3A, and TET2, were low, being present in 1.5%, 0.7%, 2.2%, and 7.5% of the total number of patients, respectively. Inv(16)/t(16;16) AML patients exhibited more mutations of NRAS and KRAS (p=0.001 and 0.0001, respectively) than t(8;21) AML patients. Functionally mutated genes involved in signaling pathways were observed more frequently in the inv(16)/t(16;16) AML group (p=0.016), while the mutations involved in cohesin were found more frequently in the t(8;21) AML group (p=0.011). Significantly higher white blood cell counts were found in inv(16)/t(16;16) AML patients with c-KIT(c-KITmut) or NRAS (NRAS(mut)) mutations compared to the corresponding t(8;21) AML/c-KITmut and t(8;21) AML/NRAS(mut) groups (p=0.001 and 0.009, respectively). Conclusion: The mutation profiles of t(8;21) AML patients showed evident differences from those of patients with inv(16)/t(16;16) AML. We have provided a comprehensive overview of the mutational landscape of CBF-AML.

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