American Association for Cancer Research
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Supplemental tables and figures from HOXA9 Cooperates with Activated JAK/STAT Signaling to Drive Leukemia Development

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journal contribution
posted on 2023-04-03, 21:44 authored by Charles E. de Bock, Sofie Demeyer, Sandrine Degryse, Delphine Verbeke, Bram Sweron, Olga Gielen, Roel Vandepoel, Carmen Vicente, Marlies Vanden Bempt, Antonis Dagklis, Ellen Geerdens, Simon Bornschein, Rik Gijsbers, Jean Soulier, Jules P. Meijerink, Merja Heinäniemi, Susanna Teppo, Maria Bouvy-Liivrand, Olli Lohi, Enrico Radaelli, Jan Cools

Supplemental tables and figures


KU Leuven


Swiss Bridge FoundationO

Tegen Kanker



Leukemia is caused by the accumulation of multiple genomic lesions in hematopoietic precursor cells. However, how these events cooperate during oncogenic transformation remains poorly understood. We studied the cooperation between activated JAK3/STAT5 signaling and HOXA9 overexpression, two events identified as significantly co-occurring in T-cell acute lymphoblastic leukemia. Expression of mutant JAK3 and HOXA9 led to a rapid development of leukemia originating from multipotent or lymphoid-committed progenitors, with a significant decrease in disease latency compared with JAK3 or HOXA9 alone. Integrated RNA sequencing, chromatin immunoprecipitation sequencing, and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) revealed that STAT5 and HOXA9 have co-occupancy across the genome, resulting in enhanced STAT5 transcriptional activity and ectopic activation of FOS/JUN (AP1). Our data suggest that oncogenic transcription factors such as HOXA9 provide a fertile ground for specific signaling pathways to thrive, explaining why JAK/STAT pathway mutations accumulate in HOXA9-expressing cells.Significance: The mechanism of oncogene cooperation in cancer development remains poorly characterized. In this study, we model the cooperation between activated JAK/STAT signaling and ectopic HOXA9 expression during T-cell leukemia development. We identify a direct cooperation between STAT5 and HOXA9 at the transcriptional level and identify PIM1 kinase as a possible drug target in mutant JAK/STAT/HOXA9-positive leukemia cases. Cancer Discov; 8(5); 616–31. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 517