Sequencing data from large cohorts of T-cell acute lymphoblastic leukemia patients identified a significant association between the presence of JAK3 mutations and ectopic HOXA9 expression. Mouse models using a constitutive or novel inducible retroviral expression vector to express the JAK3(M511I) mutant and HOXA9 led to the development of an aggressive leukemia in vivo, with shorter latency than JAK3(M511I) or HOXA9 alone. This was primarily due to the co-binding of STAT5 and HOXA9 to the same genomic loci leading to increased oncogenic JAK-STAT signaling.
Keywords: leukemia; retroviral vector; signaling; transcription factor.