Comprehensive Mutation Profile in Acute Myeloid Leukemia Patients with RUNX1-RUNX1T1 or CBFB-MYH11 FusionsWei Qin1, Xiayu Chen2, Hong Jie Shen3, Zheng Wang4, Xiaohui Cai1, Naike Jiang1, Haiying Hua21Affiliated Changzhou Second Hospital of Nanjing Medical University, Department of Hematology, Changzhou, China
2Affiliated Hospital of Jiangnan University, Department of Hematology, Wuxi, China
3The First Affiliated Hospital of Soochow University, Department of Hematology, Soochow, China
4Suzhou Jsuniwell Medical Laboratory, Suzhou, China
Objective: This study was undertaken with the aim of better understanding the genomic landscape of core-binding factor (CBF) acute myeloid leukemia (AML).
Materials and Methods: We retrospectively analyzed 112 genes that were detected using next-generation sequencing in 134 patients with de novo CBF-AML. FLT3-ITD, NPM1, and CEBPA mutations were detected by DNA-PCR and Sanger sequencing.
Results: In the whole cohort, the most commonly mutated genes were c-KIT (33.6%) and NRAS (33.6%), followed by FLT3 (18.7%), KRAS (13.4%), RELN (8.2%), and NOTCH1 (8.2%). The frequencies of mutated genes associated with epigenetic modification, such as IDH1, IDH2, DNMT3A, and TET2, were low, being present in 1.5%, 0.7%, 2.2%, and 7.5% of the total number of patients, respectively. Inv(16)/t(16;16) AML patients exhibited more mutations of NRAS and KRAS (p=0.001 and 0.0001, respectively) than t(8;21) AML patients. Functionally mutated genes involved in signaling pathways were observed more frequently in the inv(16)/t(16;16) AML group (p=0.016), while the mutations involved in cohesin were found more frequently in the t(8;21) AML group (p=0.011). Significantly higher white blood cell counts were found in inv(16)/t(16;16) AML patients with c-KIT (c-KITmut) or NRAS (NRASmut) mutations compared to the corresponding t(8;21) AML/c-KITmut and t(8;21) AML/NRASmut groups (p=0.001 and 0.009, respectively).
Conclusion: The mutation profiles of t(8;21) AML patients showed evident differences from those of patients with inv(16)/t(16;16) AML. We have provided a comprehensive overview of the mutational landscape of CBF-AML.
Keywords: Core-binding factor, Acute myeloid leukemia, Mutation, Next-generation sequencing
RUNX1-RUNX1T1 veya CBFB-MYH11 Füzyonları Olan Akut Myeloid Lösemili Hastalarda Detaylı Mutasyon ProfiliWei Qin1, Xiayu Chen2, Hong Jie Shen3, Zheng Wang4, Xiaohui Cai1, Naike Jiang1, Haiying Hua21Affiliated Changzhou Second Hospital of Nanjing Medical University, Department of Hematology, Changzhou, China
2Affiliated Hospital of Jiangnan University, Department of Hematology, Wuxi, China
3The First Affiliated Hospital of Soochow University, Department of Hematology, Soochow, China
4Suzhou Jsuniwell Medical Laboratory, Suzhou, China
Amaç: Bu çalışma çekirdek bağlama faktörü (ÇBF) akut myeloid löseminin (AML) genomik durumunu daha iyi anlamak amacıyla yapılmıştır.
Gereç ve Yöntem: Yüz otuz dört de novo ÇBF-AML hastasında yeni nesil dizileme ile tespit edilen 112 geni geriye dönük olarak analiz ettik. FLT3-ITD, NPM1 ve CEBPA mutasyonları DNA-PCR ve Sanger dizileme ile tespit edildi.
Bulgular: Bütün kohortta en sık mutasyonlu genler c-KIT (33,6%) ve NRAS (33,6%) ve ardından FLT3 (%18,7), KRAS (%13,4), RELN (%8,2), NOTCH1 (%8,2) idi. IDH1, IDH2, DNMT3A ve TET2 gibi epigenetik modifikasyonla ilişkili mutasyona uğramış genlerin sıklığı düşüktü ve toplam hastaların sırasıyla %1,5, %0,7, %2,2 ve %7,5’inde mevcuttu. Inv(16)/t(16;16) AML hastalarında NRAS ve KRAS mutasyonları t(8;21) AML hastalarına göre daha fazlaydı (sırasıyla; p=0,001; 0,0001). İşlevsel olarak sinyal yolaklarında yer alan mutasyonlu genler inv(16)/t(16;16) AML grubunda daha çok gözlenirken (p=0,016), kohezin içinde yer alan mutasyonlar t(8;21) AML grubunda daha çok bulundu (p=0,011). c-KIT (c-KITmut) veya NRAS mutasyonları (NRASmut) olan inv(16)/t(16;16) AML hastalarında karşılığındaki t(8;21) AML/c-KITmut ve t(8;21) AML/NRASmut gruplarına göre beyaz küre sayısı daha yüksek bulundu (sırasıyla; p=0,001; 0,009,).
Sonuç: t(8;21) AML hastalarının mutasyon profilleri inv(16)/t(16;16) AML’den belirgin farklılıklar gösterdi. Bu çalışmada ÇBF-AML’nin mutasyon profili kapsamlı bir biçimde incelenmiştir.
Anahtar Kelimeler: Çekirdek bağlama faktörü, Akut myeloid lösemi, Mutasyon, Yeni nesil sekanslama
Wei Qin, Xiayu Chen, Hong Jie Shen, Zheng Wang, Xiaohui Cai, Naike Jiang, Haiying Hua. Comprehensive Mutation Profile in Acute Myeloid Leukemia Patients with RUNX1-RUNX1T1 or CBFB-MYH11 Fusions. Turk J Hematol. 2022; 39(2): 84-93
Corresponding Author: Naike Jiang, China |
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