Yıl: 2024 Cilt: 44 Sayı: 2 Sayfa Aralığı: 69 - 75 Metin Dili: İngilizce DOI: 10.5336/medsci.2023-98368 İndeks Tarihi: 10-06-2024

The Incidence of BRAF V600E Mutations and the Impact of Cladribine Treatment on the Incidence of BRAF V600E Mutations and Survival in Hairy Cell Leukemia Patients: A Case-Control Study

Öz:
Objective: Hairy cell leukemia (HCL) is a rare and indolent lym- phoproliferative disease characterized by the infiltration of hairy shaped leukemic B cells with specific immunophenotypic features in the bone marrow, spleen and liver resulting in progressive pancytopenia and splenomegaly. Purine analogs are preferred as the first-line treatment for HCL. This study investigates the signifi- cance of BRAF V600E mutations in HCL diagnosis and prognosis, focusing on their baseline and post-cladribine treatment incidences and impacts on patient survival. Material and Methods: This retrospective, case-control study com- prises HCL patients diagnosed and treated between July 2012 and June 2014. The study group includes 22 HCL patients (newly diagnosed n=10, remission n=12). The control group comprises B-cell chronic lymphoproliferative disease patients (n=10). All HCL patients underwent cladribine treatment. Patient demographics, clinical characteristics, and survival outcomes were recorded.Results: The mean age of the predominantly male (81.8%) study group was 51.1±10.2 years. No sig- nificant differences in demographic and clinical features existed between the groups (p>0.05). The incidence of BRAF V600E mutation among HCL patients, initially 69.2%, fell to 20% post-treatment. Yet, no significant disparity in over- all survival and mortality rates was found between HCL patients with/without BRAF V600E mutation (p=0.256 and p=0.999). Conclusion: The proportion of HCL patients with BRAF V600E mutations decreased from 69.2% to 20% post- cladribine. However, persistence of the mutation didn’t significantly affect HCL patient survival and mortality.
Anahtar Kelime: Hairy cell leukemia BRAF V600E mutation cladribine mortality rate survival

Tüylü Hücreli Lösemi Hastalarında BRAF V600E Mutasyonu Sıklığı ve Kladribin Tedavisinin Mutasyon Sıklığı ve Sağkalım Üzerindeki Etkisi: Bir Vaka Kontrol Çalışması

Öz:
Amaç: Tüylü hücreli lösemi [hairy cell leukemia (HCL)] splenomegali ve ilerleyici pansitopeni ile seyreden, kemik ili ği, dalak ve karaciğerin tüylü görü- nümlü lösemik B hücreleri ile infiltre oldu ğu, yavaş seyirli, spesifik immünofe- notipik bulgulara sahip, nadir görülen bir hastal ıktır. Günümüzde, HCL’nin tedavisinde ilk basamakta pürin analoglar ı tercih edilmektedir. Bu çal ışmada, BRAF V600E mutasyonunun HCL tan ı ve prognozundaki önemi, kladribin te- davisi öncesi ve sonrası insidansları ve hasta sağkalımı üzerine etkileri araştırıl- maktadır. Gereç ve Yöntemler: Bu retrospektif vaka-kontrol çal ışmasının popülasyonu, Temmuz 2012-Haziran 2014 aras ında tanı ve tedavi gören HCL hastalarından oluşmaktadır. Çalışma grubu 22 HCL hastasını (yeni tanı n=10, re- misyon n=12) içerirken, kontrol grubu B hücreli kronik lenfoproliferatif hastalığı olan hastaları (n=10) kapsamaktadır. Tüm HCL hastalarına kladribin tedavisi uy- gulanmıştır. Hastaların demografik ve klinik özellikleri kaydedilmi ştir. Bulgu- lar: Çalışma grubu, ağırlıklı olarak erkek (%81,8) ve ortalama yaş 51,1±10,2 idi. Gruplar arasında demografik ve klinik özelliklerde anlamlı bir fark bulunmamış- tır (p>0,05). Başlangıçtaki BRAF V600E mutasyonu pozitifliği oranı %69,2 iken, tedavi sonrası %20’ye düşmüştür. Ancak BRAF V600E mutasyonu olan ve ol- mayan HCL hastalar ı arasında genel sa ğkalım ve ölüm oranlar ında belirgin bir fark görülmemi ştir (p=0,256 ve p=0,999). Sonuç: Kladribin tedavisi sonras ı BRAF V600E mutasyonlu HCL hastalarının oranı %69,2’den %20’ye düşmüştür. Ancak kladribin tedavisi sonrası mutasyonda negatifleşmenin HCL hastalarında sağkalım ve mortalite üzerinde anlamlı bir etkisi bulunmamaktadı
Anahtar Kelime: Tüylü hücreli lösemi BRAF V600E mutasyonu kladribin ölüm oranı sağkalım

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
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  • 1. Bibi A, Java S, Chaudhary S, Joshi S, Mascerhenas R, Rabade N, et al. BRAFV600E mutation in hairy cell leukemia: A single-center experience. In- dian J Pathol Microbiol. 2018;61(4):532-6. [Crossref] [PubMed]
  • 2. So CC, Chan A, Chung LP, Siu L, Wong WS, Wong KF. A comparison of high resolution melting, allele-specific priming and Sanger sequencing for the de- tection of BRAFV600E mutation in hairy cell leukaemia from different haema- tological specimens. Pathology. 2014;46(6):533-7. [Crossref] [PubMed]
  • 3. Tiacci E, Schiavoni G, Forconi F, Santi A, Trentin L, Ambrosetti A, et al. Sim- ple genetic diagnosis of hairy cell leukemia by sensitive detection of the BRAF-V600E mutation. Blood. 2012;119(1):192-5. Erratum in: Blood. 2013;122(9):1685. [Crossref] [PubMed]
  • 4. Schnittger S, Bacher u, Haferlach T, Wendland N, ulke M, Dicker F, et al. Development and validation of a real-time quantification assay to detect and monitor BRAFV600E mutations in hairy cell leukemia. Blood. 2012;119(13):3151-4. [Crossref] [PubMed]
  • 5. Durham BH, Getta B, Dietrich S, Taylor J, Won H, Bogenberger JM, et al. Genomic analysis of hairy cell leukemia identifies novel recurrent genetic al- terations. Blood. 2017;130(14):1644-8. [Crossref] [PubMed] [PMC]
  • 6. Maitre E, Cornet E, Debliquis A, Drenou B, Gravey F, Chollet D, et al. Hairy cell leukemia: a specific 17-gene expression signature points to new targets for therapy. J Cancer Res Clin Oncol. 2022;148(8):2013-22. [Crossref] [PubMed] [PMC]
  • 7. Gupta R, Yadav S, Mittal N, Rahman K, Sharma A, Gupta A, et al. Clinico- pathological spectrum of hairy-cell leukemia: A single-center study with brief review of Indian literature. J Cancer Res Ther. 2020;16(1):120-26. [Crossref] [PubMed]
  • 8. Tadmor T, Tiacci E, Falini B, Polliack A. The BRAF-V600E mutation in hema- tological malignancies: a new player in hairy cell leukemia and Langerhans cell histiocytosis. Leuk Lymphoma. 2012;53(12):2339-40. [Crossref] [PubMed]
  • 9. Tiacci E, Trifonov V, Schiavoni G, Holmes A, Kern W, Martelli MP, et al. BRAF mutations in hairy-cell leukemia. N Engl J Med. 2011;364(24):2305-15. [Crossref] [PubMed] [PMC]
  • 10. Chung SS, Kim E, Park JH, Chung YR, Lito P, Teruya-Feldstein J, et al. Hematopoietic stem cell origin of BRAFV600E mutations in hairy cell leukemia. Sci Transl Med. 2014;6(238):238ra71. [Crossref] [PubMed] [PMC]
  • 11. Maitre E, Bertrand P, Maingonnat C, Viailly PJ, Wiber M, Naguib D, et al. New generation sequencing of targeted genes in the classical and the variant form of hairy cell leukemia highlights mutations in epigenetic regulation genes. On- cotarget. 20182;9(48):28866-76. [Crossref] [PubMed] [PMC]
  • 12. Smirnova SY, Al-Radi LS, Moiseeva TN, Gemdzhian EG, Yakutik IA, Jul- hakyan HL, et al. Inhibitor of BRAFV600E Mutation as a Treatment Option for Hairy Cell Leukemia With Deep Neutropenia and Infectious Complications. Clin Lymphoma Myeloma Leuk. 2021;21(7):427-30. [Crossref] [PubMed]
  • 13. Zhang R, Wu Y, Wang X, Lu X, Li Y, Li S, et al. Difference of genomic copy numbers alterations between hairy cell leukemia-variant and classical hairy cell leukemia: a pilot retrospective study in Chinese. Int J Med Sci. 2020;17(3):325-31. [Crossref] [PubMed] [PMC]
  • 14. Gozzetti A, Sammartano V, Bacchiarri F, Raspadori D, Bocchia M. A BRAF- Negative Classic Hairy Cell Leukemia Patient with Long-Lasting Complete Remission after Rituximab and Pentostatin. Turk J Haematol. 2020;37(4):286- 7. [Crossref] [PubMed] [PMC]
  • 15. Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117(19):5019-32. [Crossref] [PubMed] [PMC]
  • 16. Andrulis M, Penzel R, Weichert W, von Deimling A, Capper D. Application of a BRAF V600E mutation-specific antibody for the diagnosis of hairy cell leukemia. Am J Surg Pathol. 2012;36(12):1796-800. [Crossref] [PubMed]
  • 17. Wang XJ, Kim A, Li S. Immunohistochemical analysis using a BRAF V600E mutation specific antibody is highly sensitive and specific for the diagnosis of hairy cell leukemia. Int J Clin Exp Pathol. 2014;7(7):4323-8.[PubMed] [PMC]
  • 18. Blombery PA, Wong SQ, Hewitt CA, Dobrovic A, Maxwell EL, Juneja S, et al. Detection of BRAF mutations in patients with hairy cell leukemia and related lymphoproliferative disorders. Haematologica. 2012;97(5):780-3. [Crossref] [PubMed] [PMC]
  • 19. Xi L, Arons E, Navarro W, Calvo KR, Stetler-Stevenson M, Raffeld M, et al. Both variant and IGHV4-34-expressing hairy cell leukemia lack the BRAF V600E mutation. Blood. 2012;119(14):3330-2. [Crossref] [PubMed] [PMC]
  • 20. Shao H, Calvo KR, Grönborg M, Tembhare PR, Kreitman RJ, Stetler-Steven- son M, et al. Distinguishing hairy cell leukemia variant from hairy cell leukemia: development and validation of diagnostic criteria. Leuk Res. 2013;37(4):401-9. [Crossref] [PubMed] [PMC]
  • 21. Wei C, Jin XX, Cai H, Wang X, Zhuang JL, Zhou DB. [Clinical and molecular characteristics and prognosis of classical hairy cell leukemia and hairy cell leukemia variant]. Zhonghua Nei Ke Za Zhi. 2023;62(4):416-21. Chinese. [PubMed]
  • 22. Maitre E, Tomowiak C, Lebecque B, Bijou F, Benabed K, Naguib D, et al. De- ciphering genetic alterations of hairy cell leukemia and hairy cell leukemia-like disorders in 98 patients. Cancers (Basel). 2022;14(8):1904. [Crossref] [PubMed] [PMC]
APA Ozmen D, Daglar Aday A, Nalcaci M, Aktan M (2024). The Incidence of BRAF V600E Mutations and the Impact of Cladribine Treatment on the Incidence of BRAF V600E Mutations and Survival in Hairy Cell Leukemia Patients: A Case-Control Study. , 69 - 75. 10.5336/medsci.2023-98368
Chicago Ozmen Deniz,Daglar Aday Aynur,Nalcaci Meliha,Aktan Melih The Incidence of BRAF V600E Mutations and the Impact of Cladribine Treatment on the Incidence of BRAF V600E Mutations and Survival in Hairy Cell Leukemia Patients: A Case-Control Study. (2024): 69 - 75. 10.5336/medsci.2023-98368
MLA Ozmen Deniz,Daglar Aday Aynur,Nalcaci Meliha,Aktan Melih The Incidence of BRAF V600E Mutations and the Impact of Cladribine Treatment on the Incidence of BRAF V600E Mutations and Survival in Hairy Cell Leukemia Patients: A Case-Control Study. , 2024, ss.69 - 75. 10.5336/medsci.2023-98368
AMA Ozmen D,Daglar Aday A,Nalcaci M,Aktan M The Incidence of BRAF V600E Mutations and the Impact of Cladribine Treatment on the Incidence of BRAF V600E Mutations and Survival in Hairy Cell Leukemia Patients: A Case-Control Study. . 2024; 69 - 75. 10.5336/medsci.2023-98368
Vancouver Ozmen D,Daglar Aday A,Nalcaci M,Aktan M The Incidence of BRAF V600E Mutations and the Impact of Cladribine Treatment on the Incidence of BRAF V600E Mutations and Survival in Hairy Cell Leukemia Patients: A Case-Control Study. . 2024; 69 - 75. 10.5336/medsci.2023-98368
IEEE Ozmen D,Daglar Aday A,Nalcaci M,Aktan M "The Incidence of BRAF V600E Mutations and the Impact of Cladribine Treatment on the Incidence of BRAF V600E Mutations and Survival in Hairy Cell Leukemia Patients: A Case-Control Study." , ss.69 - 75, 2024. 10.5336/medsci.2023-98368
ISNAD Ozmen, Deniz vd. "The Incidence of BRAF V600E Mutations and the Impact of Cladribine Treatment on the Incidence of BRAF V600E Mutations and Survival in Hairy Cell Leukemia Patients: A Case-Control Study". (2024), 69-75. https://doi.org/10.5336/medsci.2023-98368
APA Ozmen D, Daglar Aday A, Nalcaci M, Aktan M (2024). The Incidence of BRAF V600E Mutations and the Impact of Cladribine Treatment on the Incidence of BRAF V600E Mutations and Survival in Hairy Cell Leukemia Patients: A Case-Control Study. Türkiye Klinikleri Tıp Bilimleri Dergisi, 44(2), 69 - 75. 10.5336/medsci.2023-98368
Chicago Ozmen Deniz,Daglar Aday Aynur,Nalcaci Meliha,Aktan Melih The Incidence of BRAF V600E Mutations and the Impact of Cladribine Treatment on the Incidence of BRAF V600E Mutations and Survival in Hairy Cell Leukemia Patients: A Case-Control Study. Türkiye Klinikleri Tıp Bilimleri Dergisi 44, no.2 (2024): 69 - 75. 10.5336/medsci.2023-98368
MLA Ozmen Deniz,Daglar Aday Aynur,Nalcaci Meliha,Aktan Melih The Incidence of BRAF V600E Mutations and the Impact of Cladribine Treatment on the Incidence of BRAF V600E Mutations and Survival in Hairy Cell Leukemia Patients: A Case-Control Study. Türkiye Klinikleri Tıp Bilimleri Dergisi, vol.44, no.2, 2024, ss.69 - 75. 10.5336/medsci.2023-98368
AMA Ozmen D,Daglar Aday A,Nalcaci M,Aktan M The Incidence of BRAF V600E Mutations and the Impact of Cladribine Treatment on the Incidence of BRAF V600E Mutations and Survival in Hairy Cell Leukemia Patients: A Case-Control Study. Türkiye Klinikleri Tıp Bilimleri Dergisi. 2024; 44(2): 69 - 75. 10.5336/medsci.2023-98368
Vancouver Ozmen D,Daglar Aday A,Nalcaci M,Aktan M The Incidence of BRAF V600E Mutations and the Impact of Cladribine Treatment on the Incidence of BRAF V600E Mutations and Survival in Hairy Cell Leukemia Patients: A Case-Control Study. Türkiye Klinikleri Tıp Bilimleri Dergisi. 2024; 44(2): 69 - 75. 10.5336/medsci.2023-98368
IEEE Ozmen D,Daglar Aday A,Nalcaci M,Aktan M "The Incidence of BRAF V600E Mutations and the Impact of Cladribine Treatment on the Incidence of BRAF V600E Mutations and Survival in Hairy Cell Leukemia Patients: A Case-Control Study." Türkiye Klinikleri Tıp Bilimleri Dergisi, 44, ss.69 - 75, 2024. 10.5336/medsci.2023-98368
ISNAD Ozmen, Deniz vd. "The Incidence of BRAF V600E Mutations and the Impact of Cladribine Treatment on the Incidence of BRAF V600E Mutations and Survival in Hairy Cell Leukemia Patients: A Case-Control Study". Türkiye Klinikleri Tıp Bilimleri Dergisi 44/2 (2024), 69-75. https://doi.org/10.5336/medsci.2023-98368