Incidence of Nucleophosmin (NPM1) and FMS-like Tyrosine Kinase (FLT3) Mutation in Adult Patients with Acute Myeloid Leukaemia (AML) and Its Influence on Survival; A Single Centre Study

INTRODUCTION: Acute Myeloid Leukaemia (AML) is a disease characterized by bone marrow failure due to increased proliferation resulting from the protection of myeloid precursor cells from differentiation and apoptosis control in the bone marrow. Nucleophosmin (NPM1) and FMS-like tyrosine kinase (FLT3) are mutations frequently seen in AML, which has heterogeneous genetics. The present study aimed to evaluate the clinical characteristics and lifespan of the patients with NPM1 and FLT3 in AML.
METHODS: The study retrospectively investigated the clinical, immunophenotypical, and genetic parameters of the patients diagnosed with AML between 1 January 2012 and 31 June 2019 in the haematology clinic of Dicle University following WHO 2016 criteria. The study primarily focused on the patients' response to the disease, genetic characteristics, and the relationship of NPM1 and FLT3 mutations with their lifespan.
RESULTS: The study was performed 107 cytogenetically normal patients were investigated using RT-PCR (Real-Time Polymerase Chain Reaction) in NMP1 and FLT3 mutations in 269 AML patients. While the median survival time in the NPM1-positive patient group was 12.3 months (95% confidence interval (C.I.): 0.1-32 months), it was 10.6 months (9%5 C.I: 4,9-16,3 months) in the NPM1-negative group. On the other hand, the median survival time in the FLT3-positive patient group was 8,4 months (95% C.I: 1,2-15,6 months), and it was 12,3 months ( 95% C.I: 3,8-20,8 months) in the FLT3-negative group. While the number of NPM1-positive patients was 31 (29%), one of the FLT3-positive patients was 19 (17.8%)
DISCUSSION AND CONCLUSION: The study found that while the NPM1 positivity rate in AML cytogenetically normal patients was 29%, the FLT3 positivity rate was 17.8%, representing the first-ever data in this respect in our country. The results indicate that overall survival was better in cases with NPM1 and worse in those with FLT3.

Akut Myeloid Lösemi (AML) Tanýlý Eriþkin Hastalarda Nükleofosmin (NPM1) ve FMS Like Tirozin Kinaz (FLT3) Mutasyonun Ýnsidansý ve Sað Kalýma Etkisi; Tek Merkez Deneyimi

GÝRÝÞ ve AMAÇ: Akut Myeloid Lösemi (AML) kemik iliðinde myeloid öncü hücrelerin diferansiyasyon ve apoptozis kontrolünden korunup proliferasyon hýzýnýn artmasý sonucu kemik iliði yetmezliði ile giden bir hastalýktýr. Nükleofosmin (NPM1) ve FMS like tirozin kinaz (FLT3), heterojen bir genetiðe sahip olan AML’de sýk görülen mutasyonlardýr. Bu çalýþmamýzda AML’de NPM1 ve FLT3 tespit edilen hastalarýn klinik özelikleri ve yaþam sürelerini deðerlendirmeyi amaçladýk.
YÖNTEM ve GEREÇLER: Çalýþmaya 01 Ocak 2012-31 Haziran 2019 tarihleri arasýnda Dicle Üniversitesi hematoloji kliniðinde WHO 2016 kriterlerine göre AML teþhisi konan hastalarýn klinik, immünofenotipik ve genetik parametreleri retrospektif olarak incelendi. Hastalarýn tedaviye cevaplarý, yaþam süreleri, genetik özelikleri ve NPM1 ve FLT3 mutasyonlarýnýn yaþam süresi ile iliþkisi incelenmiþtir.
BULGULAR: Çalýþmamýzda 269 AML tanýsý alan hastalardan 'sitogenetik olarak normal 107 hasta RT-PCR (Gerçek Zamanlý Polimeraz Zincir Reaksiyonu) kullanýlarak NMP1 ve FLT3 mutasyonlarýnda araþtýrýldý.. NPM1 pozitif hasta grubunda ortanca saðkalým 12,3 ay (% 95 confidence interval(C.I.): 0,1-32 ay) tespit edildi, NPM1 negatif hasta grubunda ise 10,6 ay(% 95 C.I: 4,9-16,3 ay) olarak tespit edildi. FLT3 pozitif hasta grubunda ortanca saðkalým süresi 8,4 ay (% 95 C.I: 1,2-15,6 ay) olup FLT3 negatif grupta ise 12,3 ay(% 95 C.I: 3,8-20,8 ay) olarak tespit edildi. NPM1 pozitif hasta sayýsý 31 (%29), FLT 3 pozitif hasta sayýsý19( % 17,8) izlendi.

TARTIÞMA ve SONUÇ: Ülkemizin ilk verisi olarak AML sitogenetik normal hastalarda NPM1 pozitiflik oraný %29, FLT3 pozitiflik oraný %17,8 bulundu. NPM1 ile genel saðkalým daha iyi, FLT3 ile genel saðkalým daha kötü olarak izlendi.