Düzeltme
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Düzeltme: Analyzing The Mutations Of Notch1 And Sf3b1 Genes In Cases With CLL Detected Isolated 13q Deletion

Yıl 2023, Cilt: 45 Sayı: 2, 480 - 484, 15.03.2023
Bu makalenin ilk hali 13 Eylül 2021 tarihinde yayımlandı. https://dergipark.org.tr/tr/pub/otd/issue/64629/916009

Düzeltme Notu

Öz

Chronic lymphocytic leukemia (CLL) is known as type of leukemia originating from clonal mature B lymphocytes and has genetic heterogeneity. Many studies have been done to clarify the genome of CLL. In these studies, del(13q) is reported as the most common chromosomal aberration. Although this anomaly is associated with good prognosis when isolated, patients have clinical heterogeneity. In addition, in many gene mutations including TP53, NOTCH1 and SF3B1 gene mutations, poor prognosis has been identified. The prognostic significance of these genes has begun to be demonstrated. According to these data, we aimed to determine the mutation rate of NOTCH1 and SF3B1 genes and to investigate the prognostic effects (disease stages, TTFT and OS) in 43 cases with isolated del(13q) by using FISH method. We investigated the most common mutations of NOTCH1 and SF3B1 gene in CLL by using Sanger sequencing method. While frameshift 7541_7542delCT mutation was detected in the NOTCH1 gene in 1 out of 42 CLL cases with clinical heterogeneity, mutation in the SF3B1 gene couldn’t be detected. As a result of our study, it was observed that NOTCH1 and SF3B1 gene mutations weren’t associated with isolated del(13q) which is compatible with the literature data. Our study is the first study that evaluates NOTCH1 and SF3B1 gene mutations with prognostic parameters of isolated del(13q) with CLL patients in the Turkish population. As a result; It was concluded that there may be different reasons responsible for the clinical heterogeneity of isolated del(13q) cases and further studies are needed to reveal these reasons

Destekleyen Kurum

ESOGÜ BAP

Proje Numarası

202011A103

Kaynakça

  • 1. Kipps TJ, Stevenson FK, Wu CJ, Croce CM, Packham G, Wierda WG, et al. Chronic lymphocytic leukaemia. Nat Rev Dis Primers. 2017;3:16096.
  • 2. Jiang Y, Chen HC, Su X, Thompson PA, Liu X, Do KA, et al. ATM function and its relationship with ATM gene mutations in chronic lymphocytic leukemia with the recurrent deletion (11q22.3-23.2). Blood Cancer J. 2016;6(9):e465.
  • 3. Fabbri G, Dalla-Favera R. The molecular pathogenesis of chronic lymphocytic leukaemia. Nat Rev Cancer. 2016;16(3):145-62.
  • 4. Tausch E, Beck P, Schlenk RF, Jebaraj BJ, Dolnik A, Yosifov DY, et al. Prognostic and predictive role of gene mutations in chronic lymphocytic leukemia: results from the pivotal phase III study COMPLEMENT1. Haematologica. 2020;105(10):2440-7.
  • 5. Durak Aras B, Isik S, Uskudar Teke H, Aslan A, Yavasoglu F, Gulbas Z, et al. Which prognostic marker is responsible for the clinical heterogeneity in CLL with 13q deletion? Mol Cytogenet. 2021;14(1):2.
  • 6. Miao Y, Miao Y, Shi K, Sun Q, Zhao SS, Xia Y, et al. A higher percentage of cells with 13q deletion predicts worse outcome in Chinese patients with chronic lymphocytic leukemia carrying isolated 13q deletion. Ann Hematol. 2018;97(9):1663-9.
  • 7. Hu B, Patel KP, Chen HC, Wang X, Luthra R, Routbort MJ, et al. Association of gene mutations with time-to-first treatment in 384 treatment-naive chronic lymphocytic leukaemia patients. Br J Haematol. 2019;187(3):307-18.
  • 8. Oscier DG, Rose-Zerilli MJ, Winkelmann N, Gonzalez de Castro D, Gomez B, Forster J, et al. The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL4 trial. Blood. 2013;121(3):468-75.
  • 9. Baliakas P, Hadzidimitriou A, Sutton LA, Rossi D, Minga E, Villamor N, et al. Recurrent mutations refine prognosis in chronic lymphocytic leukemia. Leukemia. 2015;29(2):329-36.
  • 10. Schwaederlé M, Ghia E, Rassenti LZ, Obara M, Dell'Aquila ML, Fecteau JF, et al. Subclonal evolution involving SF3B1 mutations in chronic lymphocytic leukemia. Leukemia. 2013;27(5):1214-7.
  • 11. Jeromin S, Weissmann S, Haferlach C, Dicker F, Bayer K, Grossmann V, et al. SF3B1 mutations correlated to cytogenetics and mutations in NOTCH1, FBXW7, MYD88, XPO1 and TP53 in 1160 untreated CLL patients. Leukemia. 2014;28(1):108-17.
  • 12. Villamor N, Conde L, Martínez-Trillos A, Cazorla M, Navarro A, Beà S, et al. NOTCH1 mutations identify a genetic subgroup of chronic lymphocytic leukemia patients with high risk of transformation and poor outcome. Leukemia. 2013;27(5):1100-6.
  • 13. Xu ZS, Zhang JS, Zhang JY, Wu SQ, Xiong DL, Chen HJ, et al. Constitutive activation of NF-κB signaling by NOTCH1 mutations in chronic lymphocytic leukemia. Oncol Rep. 2015;33(4):1609-14.
  • 14. Pérez C. C. R-VEA, Hernández-Sánchez M., Quijada-Álamo M., Benito R., Hernández-Sánchez J., Martín-Izquierdo M., … & Hernández Rivas J. Notch1, Tp53, Sf3b1, Atm And Bırc3 Gene Mutatıons Are Assocıated Wıth A Worse Outcome In Chronıc Lymphocytıc Leukemıa Patıents Wıth 13q Losses. European Hematology Association 2018.

Düzeltme: İzole 13q Delesyonu Saptanan KLL Olgularında Notch1 ve Sf3b1 Genlerinde Mutasyon Analizi

Yıl 2023, Cilt: 45 Sayı: 2, 480 - 484, 15.03.2023
Bu makalenin ilk hali 13 Eylül 2021 tarihinde yayımlandı. https://dergipark.org.tr/tr/pub/otd/issue/64629/916009

Düzeltme Notu

"This work has been supported by Eskisehir Osmangazi University Scientific Research Projects Coordination Unit under grant number #167"

Öz

Kronik lenfositik lösemi (KLL) klonal matür B lenfositten kaynaklanan ve genetik heterojenite gösteren bir lösemi tipi olarak bilinmektedir. KLL’nin genomunun aydınlatılması için birçok çalışma yapıldığı görülmektedir. Bu çalışmalarda, kromozomal aberasyonlardan en sık del(13q)’nun meydana geldiği bildirilmektedir. Bu anomali izole olduğu durumda iyi prognoz ile ilişkilendirilmesine rağmen, hastalar klinik heterojenite göstermektedir. Bunun yanında kötü prognoz ile ilişkilendirilen TP53, NOTCH1 ve SF3B1 gen mutasyonlarının da bulunduğu bir çok gende mutasyonlar tanımlanmış ve prognostik önemleri ortaya koyulmaya başlanmıştır. Biz de, bu veriler doğrultusunda FISH yöntemiyle izole del(13q) saptadığımız 43 olguda NOTCH1 ve SF3B1 genlerinin mutasyon oranını belirlemeyi ve prognoza (hastalık evreleri, TTFT ve OS) olan etkisini araştırmayı hedefledik. KLL’de en sık gözlenen NOTCH1 ve SF3B1 gen mutasyonlarını Sanger sekanslama yöntemi ile araştırdık. Klinik heterojeniteye sahip KLL olgu grubumuzun, 1/42’sinde NOTCH1 geninde frameshift 7541_7542delCT mutasyonu saptanırken, SF3B1 geninde mutasyon tespit edemedik. Çalışmamız sonucunda, NOTCH1 ve SF3B1 gen mutasyonlarının literatür verileri ile uyumlu olarak izole del(13q) ile ilişkili olmadığı gözlenmiştir. Çalışmamız Türk populasyonunda izole del(13q) KLL hastalarında prognostik parametreler ile birlikte NOTCH1 ve SF3B1 gen mutasyonlarının değerlendirildiği ilk çalışma olma özelliğindedir. Sonuç olarak; izole del(13q) vakalarının klinik heterojenitesinden sorumlu başka nedenlerin de olabileceği ve bunların ortaya çıkarılmasını amaçlayan daha fazla çalışmaya ihtiyaç olduğu sonucuna varılmıştır.

Proje Numarası

202011A103

Kaynakça

  • 1. Kipps TJ, Stevenson FK, Wu CJ, Croce CM, Packham G, Wierda WG, et al. Chronic lymphocytic leukaemia. Nat Rev Dis Primers. 2017;3:16096.
  • 2. Jiang Y, Chen HC, Su X, Thompson PA, Liu X, Do KA, et al. ATM function and its relationship with ATM gene mutations in chronic lymphocytic leukemia with the recurrent deletion (11q22.3-23.2). Blood Cancer J. 2016;6(9):e465.
  • 3. Fabbri G, Dalla-Favera R. The molecular pathogenesis of chronic lymphocytic leukaemia. Nat Rev Cancer. 2016;16(3):145-62.
  • 4. Tausch E, Beck P, Schlenk RF, Jebaraj BJ, Dolnik A, Yosifov DY, et al. Prognostic and predictive role of gene mutations in chronic lymphocytic leukemia: results from the pivotal phase III study COMPLEMENT1. Haematologica. 2020;105(10):2440-7.
  • 5. Durak Aras B, Isik S, Uskudar Teke H, Aslan A, Yavasoglu F, Gulbas Z, et al. Which prognostic marker is responsible for the clinical heterogeneity in CLL with 13q deletion? Mol Cytogenet. 2021;14(1):2.
  • 6. Miao Y, Miao Y, Shi K, Sun Q, Zhao SS, Xia Y, et al. A higher percentage of cells with 13q deletion predicts worse outcome in Chinese patients with chronic lymphocytic leukemia carrying isolated 13q deletion. Ann Hematol. 2018;97(9):1663-9.
  • 7. Hu B, Patel KP, Chen HC, Wang X, Luthra R, Routbort MJ, et al. Association of gene mutations with time-to-first treatment in 384 treatment-naive chronic lymphocytic leukaemia patients. Br J Haematol. 2019;187(3):307-18.
  • 8. Oscier DG, Rose-Zerilli MJ, Winkelmann N, Gonzalez de Castro D, Gomez B, Forster J, et al. The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL4 trial. Blood. 2013;121(3):468-75.
  • 9. Baliakas P, Hadzidimitriou A, Sutton LA, Rossi D, Minga E, Villamor N, et al. Recurrent mutations refine prognosis in chronic lymphocytic leukemia. Leukemia. 2015;29(2):329-36.
  • 10. Schwaederlé M, Ghia E, Rassenti LZ, Obara M, Dell'Aquila ML, Fecteau JF, et al. Subclonal evolution involving SF3B1 mutations in chronic lymphocytic leukemia. Leukemia. 2013;27(5):1214-7.
  • 11. Jeromin S, Weissmann S, Haferlach C, Dicker F, Bayer K, Grossmann V, et al. SF3B1 mutations correlated to cytogenetics and mutations in NOTCH1, FBXW7, MYD88, XPO1 and TP53 in 1160 untreated CLL patients. Leukemia. 2014;28(1):108-17.
  • 12. Villamor N, Conde L, Martínez-Trillos A, Cazorla M, Navarro A, Beà S, et al. NOTCH1 mutations identify a genetic subgroup of chronic lymphocytic leukemia patients with high risk of transformation and poor outcome. Leukemia. 2013;27(5):1100-6.
  • 13. Xu ZS, Zhang JS, Zhang JY, Wu SQ, Xiong DL, Chen HJ, et al. Constitutive activation of NF-κB signaling by NOTCH1 mutations in chronic lymphocytic leukemia. Oncol Rep. 2015;33(4):1609-14.
  • 14. Pérez C. C. R-VEA, Hernández-Sánchez M., Quijada-Álamo M., Benito R., Hernández-Sánchez J., Martín-Izquierdo M., … & Hernández Rivas J. Notch1, Tp53, Sf3b1, Atm And Bırc3 Gene Mutatıons Are Assocıated Wıth A Worse Outcome In Chronıc Lymphocytıc Leukemıa Patıents Wıth 13q Losses. European Hematology Association 2018.
Toplam 14 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm ORİJİNAL MAKALELER / ORIGINAL ARTICLES
Yazarlar

Gülçin Günden 0000-0003-1707-1764

Sevgi Işık 0000-0003-0243-784X

Hava Üsküdar Teke 0000-0002-4434-4580

Oğuz Çilingir 0000-0002-5593-4164

Nur Oguz Davutoglu 0000-0003-3898-3527

Ebru Erzurumluoğlu 0000-0002-1275-5174

Sinem Kocagil Bu kişi benim 0000-0003-2595-3919

Sevilhan Artan 0000-0001-7658-6309

Beyhan Durak Aras 0000-0003-1881-1912

Proje Numarası 202011A103
Yayımlanma Tarihi 15 Mart 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 45 Sayı: 2

Kaynak Göster

Vancouver Günden G, Işık S, Üsküdar Teke H, Çilingir O, Oguz Davutoglu N, Erzurumluoğlu E, Kocagil S, Artan S, Durak Aras B. Analyzing The Mutations Of Notch1 And Sf3b1 Genes In Cases With CLL Detected Isolated 13q Deletion. Osmangazi Tıp Dergisi. 2023;45(2):480-4.


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