ETV6::ACSL6 translocation-driven super-enhancer activation leads to eosinophilia in acute lymphoblastic leukemia through IL-3 overexpression

• Published in: Haematologica (Roma) Vol. 109; no. 8; pp. 2445 - 2458
• Main Authors: Xu, Wenqian, Tian, Feng, Tai, Xiaolu, Song, Gaoxian, Liu, Yuanfang, Fan, Liquan, Weng, Xiangqin, Yang, Eunjeong, Wang, Meng, Bornhäuser, Martin, Zhang, Chao, Lock, Richard B., Wong, Jason W.H., Wang, Jin, Jing, Duohui, Mi, Jian-Qing
• Format: Journal Article
• Language: English
• Published: Italy Fondazione Ferrata Storti 01.08.2024; Ferrata Storti Foundation
• Subjects: Acute Lymphoblastic Leukemia; Animals; Enhancer Elements, Genetic; Eosinophilia - genetics; Eosinophilia - metabolism; Eosinophilia - pathology; ETS Translocation Variant 6 Protein; Gene Expression Regulation, Leukemic; Humans; Interleukin-3 - genetics; Interleukin-3 - metabolism; Mice; Oncogene Proteins, Fusion - genetics; Oncogene Proteins, Fusion - metabolism; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Proto-Oncogene Proteins c-ets - genetics; Proto-Oncogene Proteins c-ets - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; Translocation, Genetic

ETV6::ACSL6 represents a rare genetic aberration in hematopoietic neoplasms and is often associated with severe eosinophilia, which confers an unfavorable prognosis requiring additional anti-inflammatory treatment. However, since the translocation is unlikely to produce a fusion protein, the mechani...