The RTK-RAS signaling pathway is enriched in patients with rare acute myeloid leukemia harboring t(16;21)(p11;q22)/ FUS::ERG

Anli Lai; Wenbing Liu; Hui Wei; Ying Wang; Dong Lin; Chunlin Zhou; Bingcheng Liu; Runxia Gu; Yan Li; Shuning Wei; Benfa Gong; Kaiqi Liu; Xiaoyuan Gong; Yuntao Liu; Guangji Zhang; Junping Zhang; Yingchang Mi; Jianxiang Wang; Shaowei Qiu

doi:10.1097/BS9.0000000000000188

The RTK-RAS signaling pathway is enriched in patients with rare acute myeloid leukemia harboring t(16;21)(p11;q22)/ FUS::ERG

Blood Sci. 2024 May 10;6(2):e00188. doi: 10.1097/BS9.0000000000000188. eCollection 2024 Apr.

Authors

Anli Lai^{1

2}, Wenbing Liu^{1

2}, Hui Wei^{1

2

3}, Ying Wang^{1

2

3}, Dong Lin^{1

2}, Chunlin Zhou^{1

2}, Bingcheng Liu^{1

2}, Runxia Gu^{1

2}, Yan Li^{1

2}, Shuning Wei^{1

2}, Benfa Gong^{1

2}, Kaiqi Liu^{1

2}, Xiaoyuan Gong^{1

2}, Yuntao Liu^{1

2}, Guangji Zhang^{1

2}, Junping Zhang^{1

2}, Yingchang Mi^{1

2

3}, Jianxiang Wang^{1

2

3}, Shaowei Qiu^{1

2

3}

Affiliations

¹ State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
² Tianjin Institutes of Health Science, Tianjin 301600, China.
³ Tianjin Key Laboratory of Cell Therapy for Blood Diseases, Tianjin 300020, China.

Abstract

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.

Keywords: Acute myeloid leukemia; BCL2; RTK-RAS signaling pathway; q22)/FUS::ERG; t(16; 21)(p11.

Copyright © 2024 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the Chinese Medical Association (CMA) and Institute of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College (IHCAMS).