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Published on: March 26, 2018
[Characterization of mutational pattern of patients with core-binding factor acute myeloid leukemia]
Jinyuan He1, Hongying Chao, Min Zhou
1The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu 213003, China. chaohy2006@126.com.
Insights
Core-binding factor acute myeloid leukemia (CBF-AML) exhibits a distinct mutational profile compared to cytogenetically normal AML. Specific gene mutations and pathway aberrations differ significantly between these AML subtypes, impacting clinical outcomes.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Acute myeloid leukemia (AML) is a heterogeneous disease with distinct genetic subtypes.
- Core-binding factor AML (CBF-AML) and cytogenetically normal AML (CN-AML) represent two major AML classifications.
- Understanding their unique mutational landscapes is crucial for targeted therapies.
Purpose of the Study:
- To comprehensively characterize the mutational profile of CBF-AML patients.
- To compare the genetic alterations in CBF-AML with those in CN-AML.
- To identify distinct molecular pathways prevalent in each AML subtype.
Main Methods:
- Analysis of 81 AML patients, including 36 CBF-AML and 45 CN-AML cases.
- Simultaneous detection of mutations in 18 key genes (e.g., FLT3, NPM1, c-KIT, TET2, CEBPA) using PCR and Sanger sequencing.
- Identification of AML1-ETO and CBFβ-MYH11 fusion genes.
Main Results:
- Mutations were detected in 83.9% of patients, with double CEBPA, NPM1, and c-KIT mutations being most frequent.
- CBF-AML showed a higher prevalence of NRAS, c-KIT, and KRAS mutations compared to CN-AML.
- CN-AML exhibited more frequent mutations in NPM1, FLT3-ITD, DNMT3A, IDH1, and CEBPA double mutations.
- Distinct pathway enrichments were observed: DNA methylation and NPM1/transcription in CN-AML, and tyrosine kinase/RAS signaling in CBF-AML.
Conclusions:
- CBF-AML and CN-AML possess significantly different genomic landscapes.
- The interplay between fusion genes and specific mutations likely influences patient prognosis and clinical presentation.
- These findings highlight the importance of subtype-specific molecular profiling in AML management.
Objective:
To characterize the mutational profile of patients with core-binding factor acute myeloid leukemia (CBF-AML).
Methods:
A total of 81 acute myeloid leukemia patients were recruited, which included 36 cases of CBF-AML and 45 cases of cytogenetically normal acute myeloid leukemia (CN-AML) . Mutations of FLT3-ITD, FLT3-TKD, NPM1, c-KIT, NRAS, KRAS, TET2, IDH1/2, RUNX1, DNMT3A, GATA2, ASjXL1, TP53, PTPN11, JAK2V617F, SETBP1 and CEBPA genes were simultaneously detected by DNA-based PCR and Sanger sequencing.
Results:
Over all, mutations were detected in 68 patients (83.9%), with the most common ones including double CEBPA mutations (n=17), followed by NPM1 (n=15), c-KIT (n=11), NRAS (n=10), TET2 (n=9), FLT3-TKD (n=9), FLT3-ITD (n=8), IDH1 (n=7), RUNX1 (n=7), KRAS (n=7), DNMT3A (n=6), IDH2 (n=4), and GATA2 (n=4) mutations. AML1-ETO and CBFβ-MYH11 fusions were present in 21 and 15 patients, respectively. Coexistence of ≥2 mutations was more common in CN-AML comparing with CBF-AML. The mutation rate of NPM1, FLT3-ITD, DNMT3A, IDH1 and CEBPA double mutations were higher in patients with CN-AML. NRAS, c-KIT and KRAS mutations were identified more frequently in patients with CBF-AML (P<0.05). Based on the function, aberration of genes involved in DNA methylation, NPM1 proteins and transcription predominated in CN-AML, while tyrosine kinase receptor signaling and RAS pathways have predominated in CBF-AML.
Conclusion:
The genomic landscape of CBF-AML patients has differed from that of CN-AML patients. Synergy of fusion genes with particular mutations may impact the clinical phenotype and prognosis of patients.
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