Main Article Content
Chronic Myeloid Leukemia, Ten Eleven Translocation 2 gene
Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. The pathogenesis of CML is based on the oncoprotein termed BCR?ABL1. TET2 initiates DNA demethylation and is frequently mutated in hematological malignancies including CML.(1) The relation between TET2 acquisition and CML transformation and/or imitinab resistance is needed to be investigated. (2)
Aim: To 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 & Method: The 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 was done using (Thermo-Fisher predesigned SNP, USA) PCR prism 7500.
Results: The mean age was 45.98±15.7 yrs in CML patients and 39.3±6.587 yrs in control group (p>0.05). TET2 SNP rs 34402524 was either heterozygous and homozygous in CML (48%,and 46.2%) but was mainly homozygous among control (80%) group (p=0.012). TET2 SNP rs 2454206 cases within CML (65.4%) and control (63.3%) group had wild patterns (p=0.046). TET2 SNP rs 61744960 showed a homozygous pattern among all groups (CML and control) showing no statistical significance (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 homozygous group had huger sizes and higher BCR-ABL1 levels 6 months after starting TKIs (p<0.05).
Conclusions/Recommendation: TET2 SNP is a common in Egyptian chronic myeloid leukemia. TET2 SNP rs 3442524 was associated with huger spleen size and higher BCR-ABL1 levels after 6 months of starting TKIs suggesting disease progression.
2. Roche-Lestienne C, Marceau A, Labis E, Nibourel O, Coiteux V, Guilhot J, et al. Mutation analysis of TET2, IDH1, IDH2 and ASXL1 in chronic myeloid leukemia. Leukemia 2011;25(10):1661-4.
3. Jabbour E, Kantarjian HJAjoh. Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring. 2018;93(3):442-59.
4. Kim T, Tyndel MS, Kim HJ, Ahn J-S, Choi SH, Park HJ, et al. Spectrum of somatic mutation dynamics in chronic myeloid leukemia following tyrosine kinase inhibitor therapy. Blood 2017;129(1):38.
5. E Solary, O A Bernard, A Tefferi, F Fuks, Vainchenker W. Ten-Eleven Translocation-2 (TET2) gene in hematopoiesis and hematopoietic diseases. Leukemia 2013:1-36.
6. Ko M, Rao A. TET2: epigenetic safeguard for HSC. Blood 2011;118(17):4501-3.
7. Albano F, Anelli L, Zagaria A, Coccaro N, Minervini A, Rossi AR, et al. Decreased TET2 gene expression during chronic myeloid leukemia progression. Leukemia research 2011;35(11):e220-e2.
8. Mohr F, Döhner K, Buske C, Rawat VPS. TET Genes: new players in DNA demethylation and important determinants for stemness. Experimental hematology 2011;39(3):272-81.
9. Ko M, Bandukwala HS, An J, Lamperti ED, Thompson EC, Hastie R, et al. Ten-Eleven-Translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice. Proceedings of the National Academy of Sciences 2011;108(35):14566-71.
10. Tan L, Shi YG. Tet family proteins and 5-hydroxymethylcytosine in development and disease. Development 2012;139:1895-902.
11. Solary E, Bernard OA, Tefferi A, Fuks F, Vainchenker W. The Ten-Eleven Translocation-2 (TET2) gene in hematopoiesis and hematopoietic diseases. Leukemia 2014;28(3):485-96.
12. Kutny MA, Alonzo TA, Gamazon ER, Gerbing RB, Geraghty D, Lange B, et al. Ethnic variation of TET2 SNP rs2454206 and association with clinical outcome in childhood AML: a report from the Children/'s Oncology Group. Leukemia 2015;29(12):2424-6.
13. Li M-J, Yang Y-L, Jou S-T, Lu M-Y, Chang H-H, Lin K-H, et al. Prevalence & Prognosis Value of TET2 Gene Polymorphisms in Childhood Acute Myeloid Leukemia in Taiwan. Blood 2011;118(21):1551.