Next-Generation Sequencing-based Genetic Landscape and its Clinical Implications for Egyptian Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome
Abstract Background Myeloid malignancies are a heterogeneous group of clonal disorders characterized by disturbed hematopoietic stem cells self-renewal, proliferation, and differentiation capacity as a result of genetic and epigenetic changes. The molecular landscape of these diseases is complex inv...
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description | Abstract
Background
Myeloid malignancies are a heterogeneous group of clonal disorders characterized by disturbed hematopoietic stem cells self-renewal, proliferation, and differentiation capacity as a result of genetic and epigenetic changes. The molecular landscape of these diseases is complex involving many molecular alterations. Several techniques have been used to identify these genetic alterations including; FISH, RT-PCR (real time-PCR) and recently next generation sequencing (NGS) that is capable of detecting copy number variations (CNV) or translocations by a fast less expensive technique making it more practical in clinical practice.
Objectives
Designing a genetic map for Egyptian population with myeloid and detecting the prognostic impact of these genetic alterations.
Patients and Methods
Myeloid NGS Oncomine 79-gene panel was applied on 42 patients diagnosed with myeloid neoplasms (Mainly AML & MDS) recruited from the hematology unit, and their follow up till 12 months.
Results
Among the different studied groups, the highest NGS variants were found in AML compared to other myeloid neoplasms, while the percentage of patients with no NGS variants is higher in MDS (77.8%). The most frequently mutated genes detected in myeloid neoplasms were NPM1 mutation in 8 patients (19%), followed by NRAS mutation in 7 patients (16.7%). BCR-ABL1 and CALR mutations were significantly more common in the MPN group (P- value =0.000). TET2 was significantly more common in MDS/MPN patients (P-value =0.027). TP53 mutation was detected in all myeloid neoplasms (Mainly in MDS) except AML (P-value =0.027). NPM1 was significantly more frequent in AML group (P-value =0.042). There was a significant correlation between the presence of NGS variants and the clinical outcome, as the presence of one or more NGS variants is associated with poor clinical outcome & lower survival rate (p value =0.038).
Conclusion
Assessment of clinically important genetic alterations by NGS is essential for the diagnosis, prognosis, monitor measurable residual disease and detect predictive mutational markers/therapeutic targets in myeloid neoplasms. However, it cannot identify structural abnormalities, so simultaneous cytogenetic analysis to have a complete picture of the genomic profile is essential. |
doi_str_mv | 10.1093/qjmed/hcae175.190 |
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Background
Myeloid malignancies are a heterogeneous group of clonal disorders characterized by disturbed hematopoietic stem cells self-renewal, proliferation, and differentiation capacity as a result of genetic and epigenetic changes. The molecular landscape of these diseases is complex involving many molecular alterations. Several techniques have been used to identify these genetic alterations including; FISH, RT-PCR (real time-PCR) and recently next generation sequencing (NGS) that is capable of detecting copy number variations (CNV) or translocations by a fast less expensive technique making it more practical in clinical practice.
Objectives
Designing a genetic map for Egyptian population with myeloid and detecting the prognostic impact of these genetic alterations.
Patients and Methods
Myeloid NGS Oncomine 79-gene panel was applied on 42 patients diagnosed with myeloid neoplasms (Mainly AML & MDS) recruited from the hematology unit, and their follow up till 12 months.
Results
Among the different studied groups, the highest NGS variants were found in AML compared to other myeloid neoplasms, while the percentage of patients with no NGS variants is higher in MDS (77.8%). The most frequently mutated genes detected in myeloid neoplasms were NPM1 mutation in 8 patients (19%), followed by NRAS mutation in 7 patients (16.7%). BCR-ABL1 and CALR mutations were significantly more common in the MPN group (P- value =0.000). TET2 was significantly more common in MDS/MPN patients (P-value =0.027). TP53 mutation was detected in all myeloid neoplasms (Mainly in MDS) except AML (P-value =0.027). NPM1 was significantly more frequent in AML group (P-value =0.042). There was a significant correlation between the presence of NGS variants and the clinical outcome, as the presence of one or more NGS variants is associated with poor clinical outcome & lower survival rate (p value =0.038).
Conclusion
Assessment of clinically important genetic alterations by NGS is essential for the diagnosis, prognosis, monitor measurable residual disease and detect predictive mutational markers/therapeutic targets in myeloid neoplasms. However, it cannot identify structural abnormalities, so simultaneous cytogenetic analysis to have a complete picture of the genomic profile is essential.</description><identifier>ISSN: 1460-2725</identifier><identifier>EISSN: 1460-2393</identifier><identifier>DOI: 10.1093/qjmed/hcae175.190</identifier><language>eng</language><publisher>Oxford University Press</publisher><ispartof>QJM : An International Journal of Medicine, 2024-10, Vol.117 (Supplement_2)</ispartof><rights>The Author(s) 2024. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com 2024</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Abdel Rahman, Nada Ahmed Hamed</creatorcontrib><creatorcontrib>Mekawy, Mohamed Amin</creatorcontrib><creatorcontrib>Hamza, Mohamed Tarif Mohamed</creatorcontrib><creatorcontrib>Moustafa, Gehan Moustafa Hamed</creatorcontrib><creatorcontrib>Agamy, Heba Samy</creatorcontrib><title>Next-Generation Sequencing-based Genetic Landscape and its Clinical Implications for Egyptian Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome</title><title>QJM : An International Journal of Medicine</title><description>Abstract
Background
Myeloid malignancies are a heterogeneous group of clonal disorders characterized by disturbed hematopoietic stem cells self-renewal, proliferation, and differentiation capacity as a result of genetic and epigenetic changes. The molecular landscape of these diseases is complex involving many molecular alterations. Several techniques have been used to identify these genetic alterations including; FISH, RT-PCR (real time-PCR) and recently next generation sequencing (NGS) that is capable of detecting copy number variations (CNV) or translocations by a fast less expensive technique making it more practical in clinical practice.
Objectives
Designing a genetic map for Egyptian population with myeloid and detecting the prognostic impact of these genetic alterations.
Patients and Methods
Myeloid NGS Oncomine 79-gene panel was applied on 42 patients diagnosed with myeloid neoplasms (Mainly AML & MDS) recruited from the hematology unit, and their follow up till 12 months.
Results
Among the different studied groups, the highest NGS variants were found in AML compared to other myeloid neoplasms, while the percentage of patients with no NGS variants is higher in MDS (77.8%). The most frequently mutated genes detected in myeloid neoplasms were NPM1 mutation in 8 patients (19%), followed by NRAS mutation in 7 patients (16.7%). BCR-ABL1 and CALR mutations were significantly more common in the MPN group (P- value =0.000). TET2 was significantly more common in MDS/MPN patients (P-value =0.027). TP53 mutation was detected in all myeloid neoplasms (Mainly in MDS) except AML (P-value =0.027). NPM1 was significantly more frequent in AML group (P-value =0.042). There was a significant correlation between the presence of NGS variants and the clinical outcome, as the presence of one or more NGS variants is associated with poor clinical outcome & lower survival rate (p value =0.038).
Conclusion
Assessment of clinically important genetic alterations by NGS is essential for the diagnosis, prognosis, monitor measurable residual disease and detect predictive mutational markers/therapeutic targets in myeloid neoplasms. However, it cannot identify structural abnormalities, so simultaneous cytogenetic analysis to have a complete picture of the genomic profile is essential.</description><issn>1460-2725</issn><issn>1460-2393</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqNUMtOwzAQtBBIlMIHcPMHkNaOnYePVVVKpfCQyj1y7U3rkjhpnIjma_hVkrbcOe3s7MysNAg9UjKhRLDpYV-Anu6UBBoFEyrIFRpRHhLPZ4Jd_-HID27RnXN7QgiPeDxCP29wbLwlWKhlY0qL13BowSpjt95GOtB4uDVG4URa7ZSsAPcAm8bheW6sUTLHq6LKezD4Hc7KGi-2XdUYafFHT4Lttd-m2eGZahvArx3kpdE4gfYLCiNPeSdSd67KpRu-rTur67KAe3STydzBw2WO0fp58Tl_8ZL35Wo-SzwVCeIFXMWaMwGaZ2GU-ULFAY1jBr7PgzjaUB1kvN9FFsqNEj6NecgpMBJIJVnExoieU1VdOldDlla1KWTdpZSkQ7_pqd_00m_a99t7ns6esq3-If8FFLqC0Q</recordid><startdate>20241001</startdate><enddate>20241001</enddate><creator>Abdel Rahman, Nada Ahmed Hamed</creator><creator>Mekawy, Mohamed Amin</creator><creator>Hamza, Mohamed Tarif Mohamed</creator><creator>Moustafa, Gehan Moustafa Hamed</creator><creator>Agamy, Heba Samy</creator><general>Oxford University Press</general><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20241001</creationdate><title>Next-Generation Sequencing-based Genetic Landscape and its Clinical Implications for Egyptian Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome</title><author>Abdel Rahman, Nada Ahmed Hamed ; Mekawy, Mohamed Amin ; Hamza, Mohamed Tarif Mohamed ; Moustafa, Gehan Moustafa Hamed ; Agamy, Heba Samy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c790-54c8d439ed4f67f29c851883e224587b1d5f48839f6abc92184641e305aca373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abdel Rahman, Nada Ahmed Hamed</creatorcontrib><creatorcontrib>Mekawy, Mohamed Amin</creatorcontrib><creatorcontrib>Hamza, Mohamed Tarif Mohamed</creatorcontrib><creatorcontrib>Moustafa, Gehan Moustafa Hamed</creatorcontrib><creatorcontrib>Agamy, Heba Samy</creatorcontrib><collection>CrossRef</collection><jtitle>QJM : An International Journal of Medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abdel Rahman, Nada Ahmed Hamed</au><au>Mekawy, Mohamed Amin</au><au>Hamza, Mohamed Tarif Mohamed</au><au>Moustafa, Gehan Moustafa Hamed</au><au>Agamy, Heba Samy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Next-Generation Sequencing-based Genetic Landscape and its Clinical Implications for Egyptian Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome</atitle><jtitle>QJM : An International Journal of Medicine</jtitle><date>2024-10-01</date><risdate>2024</risdate><volume>117</volume><issue>Supplement_2</issue><issn>1460-2725</issn><eissn>1460-2393</eissn><abstract>Abstract
Background
Myeloid malignancies are a heterogeneous group of clonal disorders characterized by disturbed hematopoietic stem cells self-renewal, proliferation, and differentiation capacity as a result of genetic and epigenetic changes. The molecular landscape of these diseases is complex involving many molecular alterations. Several techniques have been used to identify these genetic alterations including; FISH, RT-PCR (real time-PCR) and recently next generation sequencing (NGS) that is capable of detecting copy number variations (CNV) or translocations by a fast less expensive technique making it more practical in clinical practice.
Objectives
Designing a genetic map for Egyptian population with myeloid and detecting the prognostic impact of these genetic alterations.
Patients and Methods
Myeloid NGS Oncomine 79-gene panel was applied on 42 patients diagnosed with myeloid neoplasms (Mainly AML & MDS) recruited from the hematology unit, and their follow up till 12 months.
Results
Among the different studied groups, the highest NGS variants were found in AML compared to other myeloid neoplasms, while the percentage of patients with no NGS variants is higher in MDS (77.8%). The most frequently mutated genes detected in myeloid neoplasms were NPM1 mutation in 8 patients (19%), followed by NRAS mutation in 7 patients (16.7%). BCR-ABL1 and CALR mutations were significantly more common in the MPN group (P- value =0.000). TET2 was significantly more common in MDS/MPN patients (P-value =0.027). TP53 mutation was detected in all myeloid neoplasms (Mainly in MDS) except AML (P-value =0.027). NPM1 was significantly more frequent in AML group (P-value =0.042). There was a significant correlation between the presence of NGS variants and the clinical outcome, as the presence of one or more NGS variants is associated with poor clinical outcome & lower survival rate (p value =0.038).
Conclusion
Assessment of clinically important genetic alterations by NGS is essential for the diagnosis, prognosis, monitor measurable residual disease and detect predictive mutational markers/therapeutic targets in myeloid neoplasms. However, it cannot identify structural abnormalities, so simultaneous cytogenetic analysis to have a complete picture of the genomic profile is essential.</abstract><pub>Oxford University Press</pub><doi>10.1093/qjmed/hcae175.190</doi></addata></record> |
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title | Next-Generation Sequencing-based Genetic Landscape and its Clinical Implications for Egyptian Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome |
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