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. 2022 Mar 1;23(3):977-984.
doi: 10.31557/APJCP.2022.23.3.977.

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

Yasser H El Nahass  1 , Heba A Nader  2 , Salwa Sabet  3 , Hend A Nooh  1 , Heba Bassiony  3 , Mahmoud Kamel  1 , Mohamed A Samra  1 , Hossam K Mahmoud  1 , Wafaa H El Metnawy  4 , Fatma A El Refaey  1
Affiliations

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

Yasser H El Nahass et al. Asian Pac J Cancer Prev. .

Abstract

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.

Keywords: ASXL1; IDH; Intermediate risk cytogenetics; acute myeloid leukemia; survival.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1.
Figure 1.
Survival Data and Outcome of AML Patients Using Kaplan-Meier Plot Showing Inferior OS in (a) ASXL1 Mutant and (b) IDH Mutant
Figure 2
Figure 2
Survival Data and Outcome of AML Patients with Intermediate Risk Cytogenetics Showing Inferior OS in (a) ASXL1 Mutant and (b) IDH Mutant
See this image and copyright information in PMC

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