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Amaç: Kronik Miyeloid Lösemi (KML), hematopoetik kök hücre (HKH) orijinli klonal miyeloproliferatif bir hastalıktır. KML’deki Bcr-Abl kimerik geni ile birlikte diğer ek mutasyonlar ve epigenetik modifikasyonlar hastalığın blastik faza doğru ilerleyişi için gereklidir. DNA metiltransferazlar (DNMTler), epigenetik olarak düzenlenmiş genlerin ifade edilmesinde ve baskılanmasında önemli rol oynayan genom metilasyonu için anahtar proteinlerdir. Hematolojik malignitelerde DNMT3A ve diğer DNA metilasyon düzenleyicilerinde mutasyonlar tanımlanmıştır. R882H mutasyonu DNMT3a’da en sık gözlenen mutasyondur. Bu çalışmanın amacı DNMT3A R882H mutasyonunun KML hastalarındaki görülme oranını araştırmaktır. Gereç ve Yöntem: Bcr/Abl kimerik gen analizi amacıyla gönderilmiş KML hastalarının kemik iliklerinden elde edilmiş olan cDNA örneklerinde, DNMT3A R882H mutasyonunu taramak için, AciI restriksiyon enzim kesimi kullanıldı. Kesim sonrası Bcr/Abl+ ve Bcr/Abl- örneklerden random seçilerek DNMT3A için DNA dizi analizi yapıldı. Elde edilen verilerin analizleri istatistiksel olarak değerlendirildi. Bulgular: 35 Bcr/Abl+ ve 60 Bcr/Abl- örneğin AciI restriksiyon enzim kesimi sonrası bu mutasyonu taşımadıkları gözlendi. Bu örneklerden random seçilerek DNA dizi analizi ile değerlendirilen örneklerde de R882H mutasyonunun olmadığı doğrulandı. Sonuç: Elde edilen sonuçlarımıza göre DNMT3A-R882H mutasyonunun KML hastalarında gözlenmediği, Bcr/Abl+ ve Bcr/Abl- bireyler arasında mutasyon görülme oranı açısından herhangi bir farklılık olmadığı gözlenmiştir. Hematopoetik hücrelerin proliferasyon potansiyelini artırmakta rol oynadığı bilinen DNMT3A R882H mutasyonunun KML progresyonu açısından etkili olmadığı ortaya konmuştur.
Chronic Myeloid Lusemia (KML) is a chronic myeloproliferative disease originating in hematopoetic root cells (HKH). Other additional mutations and epigenetic modifications, along with the Bcr-Abl chemical gene in KML, are necessary for the progression of the disease towards the blastic phase. DNA methyltransferases (DNMTs) are key proteins for genom methylation, which play an important role in the expression and printing of epigenetically regulated genes. In hematological malignities, mutations are identified in DNMT3A and other DNA methylation regulators. The R882H mutation is the mutation observed by DNMT3a. The aim of this study is to investigate the incidence rate of DNMT3A R882H mutation in KML patients. In cDNA samples, which were obtained from the bone marrow of KML patients sent for the purpose of chemical gene analysis, the DNMT3A R882H mutation was scanned, the AciI restriction enzyme cut was used. The DNA series for DNMT3A was randomly selected from Bcr/Abl+ and Bcr/Abl- samples. The analysis of the data received was statistically assessed. The findings: 35 Bcr/Abl+ and 60 Bcr/Abl—for example, the AciI restriction enzyme cut after this mutation was not observed. These samples were randomly selected and evaluated by DNA series analysis and confirmed that there was no R882H mutation. The result: Our findings show that DNMT3A-R882H mutation was not observed in KML patients, and that there was no difference in mutation rates between Bcr/Abl+ and Bcr/Abl- individuals. The known DNMT3A R882H mutation in which hematopoetic cells play a role in increasing proliferation potential has not been shown to be effective in terms of KML progression.
Objective: Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disease of hematopoietic stem cell (HKH) origin. Along with the Bcr-Abl chimeric gene in KML, other additional mutations and epigenetic modifications are necessary for the disease to progress to the blastic phase. DNA methyltransferases (DNMTs) are key proteins for genome methylation, which play an important role in the expression and suppression of epigenetically regulated genes. Mutations in DNMT3A and other DNA methylation regulators have been identified in hematological malignancies. R882H mutation is the most common mutation in DNMT3a. The aim of this study is to investigate the incidence of DNMT3A R882H mutation in CML patients. Materials and Methods: AciI restriction enzyme cutting was used to screen the DNMT3A R882H mutation in cDNA samples obtained from bone marrow samples of CML patients sent for Bcr/Abl chimeric gene analysis. DNA sequence analysis was performed for DNMT3A after random selection from Bcr/Abl + and Bcr/Abl- samples after cutting. Analyzes of the data obtained were evaluated statistically. Results: It was observed that 35 Bcr/Abl + and 60 Bcr/Abl- samples did not carry this mutation after AciI restriction enzyme cutting. It was confirmed that there was no R882H mutation in the samples evaluated randomly by DNA sequence analysis from these samples. Conclusion: According to our results, it was founded that DNMT3A-R882H mutation was not observed in CML patients and there was no difference in the rate of mutation among Bcr/Abl + and Bcr/Abl- individuals. It has been demonstrated that the DNMT3A R882H mutation, which is known to play a role in increasing the proliferation potential of hematopoietic cells, is not effective for CML progression.
Alan : Sağlık Bilimleri
Dergi Türü : Ulusal
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