TY - JOUR
T1 - ETNK1 mutation occurs in a wide spectrum of myeloid neoplasms and is not specific for atypical chronic myeloid leukemia
AU - Shuai, Wen
AU - Zuo, Zhuang
AU - Li, Nianyi
AU - Garces, Sofia
AU - Jelloul, Fatima Zahra
AU - Ok, Chi Young
AU - Li, Shaoying
AU - Xu, Jie
AU - You, M. James
AU - Wang, Wei
AU - Rehder, Catherine
AU - Jabbour, Elias J.
AU - Patel, Keyur P.
AU - Medeiros, L. Jeffrey
AU - Yin, C. Cameron
N1 - Funding Information:
Chi Young Ok reports grants from Seattle Genetics outside the submitted work. Catherine Rehder reports personal fees from Alexon Pharmaceuticals and Amicus Therapeutics, Inc., outside the submitted work. Elias J. Jabbour reports personal fees from Takeda Oncology, Adaptive Biotechnology Corporation, AbbVie, Novartis, Amgen, Pfizer Canada Inc., and Bristol‐Myers Squibb outside the submitted work. The remaining authors made no disclosures.
Publisher Copyright:
© 2022 American Cancer Society.
PY - 2023/3/15
Y1 - 2023/3/15
N2 - Background: 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. Methods: The authors assessed the clinicopathologic and molecular genetic features of 80 ETNK1-mutated myeloid neoplasms. Results: 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. Conclusions: 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.
AB - Background: 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. Methods: The authors assessed the clinicopathologic and molecular genetic features of 80 ETNK1-mutated myeloid neoplasms. Results: 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. Conclusions: 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.
KW - acute myeloid leukemia (AML), ethanolamine kinase 1 (ETNK1), myelodysplastic syndrome (MDS), myelodysplastic/myeloproliferative neoplasm (MDS/MPN), myeloproliferative neoplasm (MPN)
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U2 - 10.1002/cncr.34616
DO - 10.1002/cncr.34616
M3 - Article
C2 - 36583229
AN - SCOPUS:85145328420
SN - 0008-543X
VL - 129
SP - 878
EP - 889
JO - Cancer
JF - Cancer
IS - 6
ER -