High Frequency of ASXL1 and IDH Mutations in Young Acute Myeloid Leukemia Egyptian Patients.

Autor:	El Nahass YH; National Cancer Institute, Cairo University, Egypt., Nader HA; Genome Onco-Center, Cairo, Egypt., Sabet S; Department of Zoology, Faculty of Science, Cairo University, Egypt., Nooh HA; National Cancer Institute, Cairo University, Egypt., Bassiony H; Department of Zoology, Faculty of Science, Cairo University, Egypt., Kamel M; National Cancer Institute, Cairo University, Egypt., Samra MA; National Cancer Institute, Cairo University, Egypt., Mahmoud HK; National Cancer Institute, Cairo University, Egypt., El Metnawy WH; Faculty of Medicine, Cairo University, Egypt., El Refaey FA; National Cancer Institute, Cairo University, Egypt.
Jazyk:	angličtina
Zdroj:	Asian Pacific journal of cancer prevention : APJCP [Asian Pac J Cancer Prev] 2022 Mar 01; Vol. 23 (3), pp. 977-984. Date of Electronic Publication: 2022 Mar 01.
DOI:	10.31557/APJCP.2022.23.3.977
Abstrakt:	Background: Prognostication of AML patients depends on association of genetic and epigenetic abnormalities. We aimed to evaluate the frequency and prognostic significance of Additional Sex comb's Like1 (ASXL1), Isocitrate Dehydrogenase (IDH) and Casitas B- lineage Lymphoma (CBL) mutations in AML assessing their association with different cytogenetic risk category. Methods: We used High Resolution Melting (HRM) technology that detects small differences in PCR amplified sequences by direct melting using EvaGreen saturating dye to analyze epigenetic mutations in 70 denovo AML patients. Results: Median age of AML patients was 39.5 years (18-75). ASXL1, IDH and CBL mutations were detected in 14 (20%), 10 (14%) and 5 (7%) patients, respectively. Mean age of ASXL1 and IDH mutants vs. wild type was 35.9±14.6 years and 42.9±14.4 years (p=0.114) and 46.7±15.2 years vs. 40.6±14.5 years (p=0.290), respectively. AML cytogenetic risk groups included low (25/70, 36%), intermediate (33/70, 47%) and high-risk (12/70, 17%). Nine/14 (64%) ASXL1 and 8/10 (80%) IDH mutants were classified as intermediate risk and 9 ASXL1 positive (64%) were adolescent and young adults (AYA). Overall survival (OS) of mutant ASXL1 vs. wild type was 1.1 years (95% CI 0.83-1.4) vs. 1.9 years (95% CI 0.71-7.51), respectively (p=0.056). OS of mutant IDH vs. wild type was 1.25 years (95% CI 0.85-1.6) vs. 1.8 years (95% CI 1.2-6.7), respectively (p=0.020). In intermediate risk cytogenetic group, ASXL1 and IDH mutants had shorter OS than wild type; 1.1 years (95% CI 0.97-1.2) vs. 2.1 years (95% CI 0.14-10.8) (p=0.002) and 1.8 years (95% CI 0.69-3.15) vs. 2.3 years (95% CI 1.1-5.5) (p=0.05), respectively. Conclusion: ASXL1 and IDH mutations occur at a high incidence among young Egyptian AML patients with intermediate risk cytogenetics and confer a poorer outcome. Integration of mutations into risk profiling may predict outcome and impact therapeutic approach of young AML patient with uncertain prognosis.
Databáze:	MEDLINE
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