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

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 ass...

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Autores principales: El Nahass, Yasser H, Nader, Heba A, Sabet, Salwa, Nooh, Hend A, Bassiony, Heba, Kamel, Mahmoud, Samra, Mohamed A, Mahmoud, Hossam K, El Metnawy, Wafaa H, El Refaey, Fatma A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: West Asia Organization for Cancer Prevention 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360955/
https://www.ncbi.nlm.nih.gov/pubmed/35345371
http://dx.doi.org/10.31557/APJCP.2022.23.3.977
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author El Nahass, Yasser H
Nader, Heba A
Sabet, Salwa
Nooh, Hend A
Bassiony, Heba
Kamel, Mahmoud
Samra, Mohamed A
Mahmoud, Hossam K
El Metnawy, Wafaa H
El Refaey, Fatma A
author_facet El Nahass, Yasser H
Nader, Heba A
Sabet, Salwa
Nooh, Hend A
Bassiony, Heba
Kamel, Mahmoud
Samra, Mohamed A
Mahmoud, Hossam K
El Metnawy, Wafaa H
El Refaey, Fatma A
author_sort El Nahass, Yasser H
collection PubMed
description 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.
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spelling pubmed-93609552022-08-10 High Frequency of ASXL1 and IDH Mutations in Young Acute Myeloid Leukemia Egyptian Patients El Nahass, Yasser H Nader, Heba A Sabet, Salwa Nooh, Hend A Bassiony, Heba Kamel, Mahmoud Samra, Mohamed A Mahmoud, Hossam K El Metnawy, Wafaa H El Refaey, Fatma A Asian Pac J Cancer Prev Research Article 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. West Asia Organization for Cancer Prevention 2022-03 /pmc/articles/PMC9360955/ /pubmed/35345371 http://dx.doi.org/10.31557/APJCP.2022.23.3.977 Text en https://creativecommons.org/licenses/by-nc/4.0/This work is licensed under a Creative Commons Attribution-Non Commercial 4.0 International License. https://creativecommons.org/licenses/by-nc/4.0/
spellingShingle Research Article
El Nahass, Yasser H
Nader, Heba A
Sabet, Salwa
Nooh, Hend A
Bassiony, Heba
Kamel, Mahmoud
Samra, Mohamed A
Mahmoud, Hossam K
El Metnawy, Wafaa H
El Refaey, Fatma A
High Frequency of ASXL1 and IDH Mutations in Young Acute Myeloid Leukemia Egyptian Patients
title High Frequency of ASXL1 and IDH Mutations in Young Acute Myeloid Leukemia Egyptian Patients
title_full High Frequency of ASXL1 and IDH Mutations in Young Acute Myeloid Leukemia Egyptian Patients
title_fullStr High Frequency of ASXL1 and IDH Mutations in Young Acute Myeloid Leukemia Egyptian Patients
title_full_unstemmed High Frequency of ASXL1 and IDH Mutations in Young Acute Myeloid Leukemia Egyptian Patients
title_short High Frequency of ASXL1 and IDH Mutations in Young Acute Myeloid Leukemia Egyptian Patients
title_sort high frequency of asxl1 and idh mutations in young acute myeloid leukemia egyptian patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360955/
https://www.ncbi.nlm.nih.gov/pubmed/35345371
http://dx.doi.org/10.31557/APJCP.2022.23.3.977
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