Turk J Hematol. 2022; 39(2): 84-93 | DOI: 10.4274/tjh.galenos.2022.2021.0641

Comprehensive Mutation Profile in Acute Myeloid Leukemia Patients with RUNX1-RUNX1T1 or CBFB-MYH11 Fusions

Wei Qin¹, Xiayu Chen², Hong Jie Shen³, Zheng Wang⁴, Xiaohui Cai¹, Naike Jiang¹, Haiying Hua^2
1Affiliated 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

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RUNX1-RUNX1T1 veya CBFB-MYH11 Füzyonları Olan Akut Myeloid Lösemili Hastalarda Detaylı Mutasyon Profili

Wei Qin¹, Xiayu Chen², Hong Jie Shen³, Zheng Wang⁴, Xiaohui Cai¹, Naike Jiang¹, Haiying Hua^2
1Affiliated 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

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