Investigation of Mutations in Chronic Myeloid Leukemia and Assessment of the Relation between Mutations and the Clinical Response

Öz

OBJECTIVE: To assess the mutation status of the patients with Chronic Myeloid Leukemia (CML) who have been treated and followed-up in our clinics and to assess the response to the treatments.METHODS: All the patients with the diagnosis of CML (n:100) were invited, 6 patients who could not be reached and 2 patients who did not want to participate were excluded. The data were gathered from files and from patient examinations. The most common 5 mutations - T315I, Y253H, E255K, E255V and M351T mutations - were assessed. Interferon-alpha, imatinib, nilotinib and dasatinib were given as first, second and third line therapies where appropriate. The disease phases, hematologic and major molecular responses, commencement time for response, new drug requirements and adverse effects were evaluated. The association between the presence of mutations and rate of the major molecular response were analyzed.RESULTS: The prevalence of the mutations in the studied population was found to be 3.3%. T315I mutation was detected in 2 patients and no response could be obtained with either nilotinib or dasatinib in these two patients. These patients were still in the accelerated phase. In one patient with M351T mutation major molecular response could not be obtained with these two drugs. Among ABL kinase domain mutations presence of T315I mutation is associated with the highest degree of resistance to imatinib, dasatinib and nilotinib. CONCLUSION: In this study it was found that presence of mutations may affect the rate of major molecular response negatively.

Anahtar Kelimeler

• Chronic Myeloid Leukemia,tyrosine kinase inhibitors,BCR-ABL

Kronik Miyeloid Lösemide Mutasyonların Araştırılması ve Klinikle Olan İlişkilerinin İncelenmesi

Öz

AMAÇ: Kliniğimizde Kronik Myeloid Lösemi (KML) tanısı ile takip ve tedavi edilen hastalarda mutasyon durumlarının incelenmesi ve verilen tedaviye olan yanıtın araştırılması.YÖNTEM: Araştırmamızda kliniğimizde takip edilen tüm KML hastaları (n:100) çalışmaya davet edilmiş, 6 hastaya ulaşılamadığından, 2 hasta da çalışmaya katılmak istemediklerinden çalışma dışı bırakılmıştır. Bu hastaların bilgilerine medikal kayıtlardan ve hasta muayenelerinden ulaşılmıştır. Hastalarda en sık görülen mutasyonlardan beş tanesi - T315I, Y253H, E255K, E255V ve M351T mutasyonları - çalışıldı. İnterferon-alfa, imatinib, nilotinib ve dasatinib uygun durumlarda birinci, ikinci ve üçüncü basamak tedavi olarak verildi. Hastalık fazı, hematolojik ve major moleküler yanıtlar, yanıt alınıncaya dek geçen zaman, yeni ilaç ihtiyacı ve yan etkiler değerlendirildi. Mutasyon varlığı ile hastalarda elde edilen majör moleküler yanıt arasındaki ilişki değerlendirildi.BULGULAR: İncelenen hasta grubunda mutasyon oranı % 3.3 olarak tespit edildi. Çalışmamızda mutasyonu olan 2 hastada T315I mutasyonu mevcut idi ve bu hastalarda nilotinib ve dasatinib tedavileri etkili olmadı. Bu hastalar halen akselere fazda idi. Yine diğer M351T mutasyonu olan hastada da bu ilaçlar ile majör moleküler yanıt elde edilemedi. ABL kinaz domain mutasyonları arasında T315I mutasyon varlığı imatinib, dasatinib ve nilotinibe en yüksek direnci gösterir. SONUÇ: Bu çalışmada da mutasyon mevcudiyetinin uygulanan tedavi ile elde edilen majör moleküler yanıt üzerine negatif etkili olabileceğini tespit edilmiştir.

Anahtar Kelimeler

• Kronik Myeloid Lösemi,Tirozin kinaz inhibitörleri,BCR-ABL

Kaynakça

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