Shuai Wen, Zuo Zhuang, Li Nianyi, Garces Sofia, Jelloul Fatima Zahra, Ok Chi Young, Li Shaoying, Xu Jie, You M James, Wang Wei, Rehder Catherine, Jabbour Elias J, Patel Keyur P, Medeiros L Jeffrey, Yin C Cameron
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Pathology, Duke University School of Medicine, Durham, North Carolina, USA.
Cancer. 2023 Mar 15;129(6):878-889. doi: 10.1002/cncr.34616. Epub 2022 Dec 29.
ETNK1 mutation has been suggested as a useful tool to support the diagnosis of atypical chronic myeloid leukemia. ETNK1 mutations, however, occur in other myeloid neoplasms.
The authors assessed the clinicopathologic and molecular genetic features of 80 ETNK1-mutated myeloid neoplasms.
Thirty-seven neoplasms (46%) were classified as myelodysplastic syndrome, 17 (21%) were classified as myelodysplastic/myeloproliferative neoplasm, 14 (18%) were classified as acute myeloid leukemia, and 12 (15%) were classified as myeloproliferative neoplasm. ETNK1 mutations were detected at the first test in 96% of patients, suggesting that ETNK1 mutation is an early event in pathogenesis. ETNK1 mutations represented the dominant clone in 63% of patients and was persistently dominant in 93%. The variant allele frequencies were usually higher in acute myeloid leukemia and increased upon leukemic transformation. ETNK1 mutation was accompanied by coexisting mutations in all patients, with ASXL1 (50%), TET2 (25%), EZH2 (24%), RUNX1 (24%), and SRSF2 (24%) mutations being the most common. Neoplasms with ETNK1 mutations were associated with morphologic dysplasia, increased blasts, myelofibrosis, and noncomplex karyotypes. With a median follow-up of 16.5 months, 30 patients died, 44 had persistent disease, and four achieved complete remission after stem cell transplantation.
ETNK1 mutation is present in various myeloid neoplasms, often as an early event and a dominant clone and always with concurrent mutations. It may play an important role in the pathogenesis and progression of myeloid neoplasms by causing DNA damage and inducing other mutations and genomic instability, and it may serve as a potential therapeutic target. ETNK1 mutation is not disease-specific and should be interpreted with caution to classify myeloid neoplasms.
ETNK1突变已被认为是支持非典型慢性髓性白血病诊断的有用工具。然而，ETNK1突变也见于其他髓系肿瘤。
作者评估了80例ETNK1突变的髓系肿瘤的临床病理和分子遗传学特征。
37例肿瘤（46%）被分类为骨髓增生异常综合征，17例（21%）被分类为骨髓增生异常/骨髓增殖性肿瘤，14例（18%）被分类为急性髓系白血病，12例（15%）被分类为骨髓增殖性肿瘤。96%的患者在首次检测时即检测到ETNK1突变，提示ETNK1突变是发病机制中的早期事件。ETNK1突变在63%的患者中代表优势克隆，在93%的患者中持续为优势克隆。急性髓系白血病中的变异等位基因频率通常较高，且在白血病转化时增加。所有患者的ETNK1突变均伴有共存突变，其中ASXL1（50%）、TET2（25%）、EZH2（24%）、RUNX1（24%）和SRSF2（24%）突变最为常见。伴有ETNK1突变的肿瘤与形态学发育异常、原始细胞增多、骨髓纤维化和核型不复杂相关。中位随访16.5个月，30例患者死亡，44例疾病持续存在，4例在干细胞移植后达到完全缓解。
ETNK1突变存在于多种髓系肿瘤中，通常是早期事件且为优势克隆，并且总是伴有并发突变。它可能通过导致DNA损伤、诱导其他突变和基因组不稳定在髓系肿瘤的发病机制和进展中起重要作用，并且可能作为潜在的治疗靶点。ETNK1突变并非疾病特异性的，在对髓系肿瘤进行分类时应谨慎解读。
