April 1, 2025

Next generation sequencing based genetic landscape and its clinical implications for Egyptian patients with acute myeloid leukemia and Myelodysplastic syndrome

NANada Ahmed Hamed AbdelRahmanAin Shams University MHMohammed Tarif HamzaQatar Airways (Qatar)GHGehan M. HamedAin Shams University

Key Points

Presence of genetic alterations was linked to poorer clinical outcomes in myeloid malignancies, indicating a need for genetic profiling.
Next generation sequencing unveiled higher mutation rates in acute myeloid leukemia compared to myelodysplastic syndrome, with NPM1 mutation being prevalent.
Prospective cohort study recruited 42 patients from Ain Shams University Hospital, assessing their genetic landscape over a 12-month follow-up.
Assessment of NGS variants provides crucial insights for the diagnosis and prognosis of myeloid neoplasms, stressing the importance of cytogenetic analysis.

Abstract

Background Myeloid malignancies are a heterogeneous group of clonal disorders characterized by disturbed hematopoietic stem cells self-renewal, proliferation, and differentiation capacity due to 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: fluorescence in situ hybridization, real time-PCR, and recently next generation sequencing (NGS) that is capable of detecting copy number variations or translocations by a fast less expensive technique making it more practical in clinical practice. Objectives Designing a genetic map for the Egyptian population with myeloid and detecting the prognostic impact of these genetic alterations. Patients and methods This is a prospective cohort clinical study conducted on 42 patients diagnosed with myeloid neoplasms (MN) Mainly Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) recruited from the hematology/oncology unit of Ain Shams University Hospital using Myeloid NGS Oncomine 79-gene panel, and their follow-up till 12 months. Results Among the different studied groups, the highest NGS variants were found in AML compared with other MN, while the percentage of patients with no NGS variants is higher in MDS (77.8%). The most frequently mutated genes detected in MN were NPM1 mutation in eight (19%) patients, followed by NRAS mutation in seven (16.7%) patients. BCR-ABL1 and CALR mutations were significantly more common in the myeloproliferative neoplasms group ( P =0.000). Tet methylcytosine dioxygenase 2 was significantly more common in MDS/myeloproliferative neoplasms patients ( P =0.027). TP53 mutation was detected in all MN (mainly in MDS) except AML ( P =0.027). NPM1 was significantly more frequent in the AML group ( P =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 and lower survival rate ( P =0.038). Conclusion Assessment of clinically important genetic alterations by NGS is essential for the diagnosis, prognosis, monitoring measurable residual disease, and detect predictive mutational markers/therapeutic targets in MN. However, it cannot identify structural abnormalities, so simultaneous cytogenetic analysis to have a complete picture of the genomic profile is essential.

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