Acute myeloid leukemia(AML)with t(16;21)(p11;q22)/FUS::ERG is a rare AML subtype associated with poor prognosis.However,its clinical and molecular features remain poorly defined.We determined the clinicopathological,g...Acute myeloid leukemia(AML)with t(16;21)(p11;q22)/FUS::ERG is a rare AML subtype associated with poor prognosis.However,its clinical and molecular features remain poorly defined.We determined the clinicopathological,genomic,and transcriptomic characteristics and outcomes of patients with AML harboring FUS::ERG at our center.Thirty-six AML patients harboring FUS::ERG were identified,with an incidence rate of 0.3%.These patients were characterized by high lactate dehydrogenase levels(median:838.5 U/L),elevated bone marrow blast counts(median:71.5%),and a CD56-positive immunophenotype(94.3%).Notably,we found that RTK–RAS GTPase(RAS)pathway genes,including NRAS(33%)and PTPN11(24%),were frequently mutated in this subtype.Transcriptome analysis revealed enrichment of the phosphatidylinositol-3-kinase-Akt(PI3K-Akt),mitogen-activated protein kinase(MAPK),and RAS signaling pathways and upregulation of BCL2,the target of venetoclax,in FUS::ERG AML compared to RUNX1::RUNX1T1 AML,a more common AML subtype with good prognosis.The median event-free survival in patients with FUS::ERG AML was 11.9(95%confidence interval[CI]:9.0–not available[NA])months and the median overall survival was 18.2(95%CI:12.4–NA)months.Allogeneic hematopoietic stem cell transplantation failed to improve outcomes.Overall,the high incidence of RTK–RAS pathway mutations and high expression of BCL2 may indicate promising therapeutic targets in this high-risk AML subset.展开更多
基金supported by the National Key Research and Development Program(2021YFC2500300)CAMS Innovation Fund for Medical Sciences(2021-I2M-1-041)+3 种基金Tianjin Municipal Science and Technology Commission Grant(23JCYBJC01050)National Natural Science Foundation of China(81830005,82000131)Clinical Research Foundation of National Clinical Research Center for Blood Diseases(2023NCRCA0101)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2022-RW320-14)。
文摘Acute myeloid leukemia(AML)with t(16;21)(p11;q22)/FUS::ERG is a rare AML subtype associated with poor prognosis.However,its clinical and molecular features remain poorly defined.We determined the clinicopathological,genomic,and transcriptomic characteristics and outcomes of patients with AML harboring FUS::ERG at our center.Thirty-six AML patients harboring FUS::ERG were identified,with an incidence rate of 0.3%.These patients were characterized by high lactate dehydrogenase levels(median:838.5 U/L),elevated bone marrow blast counts(median:71.5%),and a CD56-positive immunophenotype(94.3%).Notably,we found that RTK–RAS GTPase(RAS)pathway genes,including NRAS(33%)and PTPN11(24%),were frequently mutated in this subtype.Transcriptome analysis revealed enrichment of the phosphatidylinositol-3-kinase-Akt(PI3K-Akt),mitogen-activated protein kinase(MAPK),and RAS signaling pathways and upregulation of BCL2,the target of venetoclax,in FUS::ERG AML compared to RUNX1::RUNX1T1 AML,a more common AML subtype with good prognosis.The median event-free survival in patients with FUS::ERG AML was 11.9(95%confidence interval[CI]:9.0–not available[NA])months and the median overall survival was 18.2(95%CI:12.4–NA)months.Allogeneic hematopoietic stem cell transplantation failed to improve outcomes.Overall,the high incidence of RTK–RAS pathway mutations and high expression of BCL2 may indicate promising therapeutic targets in this high-risk AML subset.
