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TET2 Single Nucleotide Polymorphism in Myeloid Neoplasms Among Egyptian Patients.

ABSTRACT: Acute myelogenous leukemia (AML) is a heterogeneous disease characterized by myeloid progenitor cells uncontrolled proliferation gradually replacing normal hematopoiesis. To evaluate Ten Eleven Translocation 2 gene (TET2) single nucleotide polymorphism (SNP) (rs2454206, rs34402524, rs61744960) in AML, and chronic myeloid leukemia (CML) in relation to their disease prognostic criteria. The study included 136 subjects; 52 AML, 54 CML and 30 subjects as control group matched for age and sex. Routine investigations including CBC, bone marrow aspiration, flow cytometry biochemical investigations and cytogenetics and molecular study were performed accordingly. DNA extraction and SNP assay for TET2 gene polymorphism was done using (Thermo-Fisher predesigned SNP, USA) PCR prism 7500. The mean age was 43.4?±?14.0 years in AML patients, 45.98?±?15.7 years in CML patients and 39.3?±?6.587 years in control group (p?>?0.05). The frequency of TET2 SNP rs 34402524 ranged from heterozygous to homozygous in both AML (46%, 54%) and CML (48%, 46.2%) groups but was mainly homozygous among the control (80%) group (p?=?0.012). TET2 SNP rs 2454206 was mainly wild in CML (65.4%) and control (63.3%) groups compared to AML as wild was only in (46%) and heterozygous in (44%) with only 10% being homozygous (p?=?0.046). TET2 SNP rs 61744960 showed a homozygous pattern among all three group (AML CML and control) showing no statistical significance (p?=?0.528). Eventhough, higher non responders to treatment were among homozygous and heterozygous groups yet, response to therapy as respect to specific TET2 SNP showed no significant variation (p?>?0.05). TET2 SNP in CML cases did not alter the prognostic criteria as no statistical significance was noted (p?>?0.05) except for TET2 SNP rs 34402524 where homozygous cases had larger spleen size (p?=?0.019). TET2 SNP is common in Egyptian myeloid neoplasm. This is the first study in this field and further studies are recommended to investigate TET2 and relation to other hematological malignancies and leukemogenesis transformation.

SUBMITTER: Dammag EA

PROVIDER: S-EPMC7042427 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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TET2 Single Nucleotide Polymorphism in Myeloid Neoplasms Among Egyptian Patients.

Dammag Enas A EA Hamed Nahla A M NAM Elhalawani Nabil A NA Kassem Heba S HS Ayad Mona W MW

Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 20190820 1

Acute myelogenous leukemia (AML) is a heterogeneous disease characterized by myeloid progenitor cells uncontrolled proliferation gradually replacing normal hematopoiesis. To evaluate Ten Eleven Translocation 2 gene (TET2) single nucleotide polymorphism (SNP) (rs2454206, rs34402524, rs61744960) in AML, and chronic myeloid leukemia (CML) in relation to their disease prognostic criteria. The study included 136 subjects; 52 AML, 54 CML and 30 subjects as control group matched for age and sex. Routin ...[more]

PMID: 32158090

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Project description:BackgroundChronic myeloid leukemia (CML) is a myeloproliferative neoplasm where pathogenesis is based on the oncoprotein termed BCR-ABL1.1 TET2 initiates DNA demethylation and is frequently mutated in hematological malignancies, including CML. The relation between TET2 acquisition and CML transformation and/or imatinib resistance is needed to be investigated.2.AimTo evaluate Ten Eleven Translocation 2 gene (TET2) single nucleotide polymorphism (SNP) (rs2454206, rs34402524, rs61744960) in chronic myeloid leukemia (CML) in relation to the disease prognostic criteria.Materials & methodThe study included 84 subjects; 54 CML in chronic phase and 30 healthy subjects as control group matched for age and sex. Routine investigations, including CBC, bone marrow aspiration, biochemical investigations, and molecular study, were performed in CML patients to identify the disease stage. DNA extraction and SNP assay for TET2 gene polymorphism were done using (Thermo-Fisher predesigned SNP, USA) PCR prism 7500.ResultsThe mean age was 45.98±15.7 yrs in CML patients and 39.3±6.587 yrs in the control group (p>0.05). TET2 SNP rs 34402524 was either heterozygous or homozygous in CML (48%, 46.2% respectively) but was mainly homozygous among control (80%) group (p=0.012). TET2 SNP rs 2454206 wild type within CML was detected in 65.4% of patients and in controls was 63.3% (p=0.046). TET2 SNP rs 61744960 showed a homozygous pattern among all groups (CML and control) (p=0.528). TET2 SNP in CML cases did not alter the prognostic criteria as no statistical significance was noted (p>0.05) yet, it was significantly related to spleen size in rs 34402524 where the homozygous group had larger spleen size and higher BCR-ABL1 levels six months after starting TKIs (p<0.05).Conclusions/recommendationTET2 SNP is common among Egyptian chronic myeloid leukemia. TET2 SNP rs 3442524 was associated with larger spleen size and higher BCR-ABL1 levels after six months of starting TKIs suggesting disease progression.

Dataset Information

TET2 Single Nucleotide Polymorphism in Myeloid Neoplasms Among Egyptian Patients.

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TET2 Single Nucleotide Polymorphism in Myeloid Neoplasms Among Egyptian Patients.

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