In vitro and in vivo modelling of mutant JAK3/STAT5 signaling in leukemia

Mutations within the IL7-R-JAK-STAT signaling pathway are important drivers of T-cell acute lymphoblastic leukemia (T-ALL). Here we describe the important steps required to generate retroviral particles for the stable expression of mutant JAK3 constructs that induce constitutive JAK/STAT signaling. These are subsequently used for the viral transduction of the IL-3 cytokine-dependent Ba/F3 cell line or murine hematopoietic stem and progenitor cells (HSPCs) for in vitro and in vivo modelling of cytokine-independent growth or leukemia initiation respectively.