1. Constitutive expression of JAK3M511I and HOXA9 leads to development of both AML and T-ALL in vivo.
Constitutive expression of JAK3M511I and HOXA9 leads to development of both AML and T-ALL in vivo. A, Representative peripheral blood FACS of expanding leukemic clones expressing JAK3M511I and HOXA9. B, Histopathology for MPO and CD3 staining of bone marrow, spleen, and lymph nodes. Scale bars: bone marrow, 40 μm; spleen and lymph nodes, 80 μm. C, Western blot analysis of spleen and bone marrow leukemic cells. D and E,Ex vivo growth assay of leukemia clones and matching FACS with JAK3M511I and HOXA9 levels measured by GFP and mCherry expression, respectively. F, Schematic of in vivo treatment of primary bone marrow transplant recipients. Mice were treated daily for 20 days from day 14 after transplantation with either 40 mg/kg/day tofacitinib (oral gavage) or vehicle control. G, Phospho-flow cytometry of pSTAT5 levels in JAK3M511I/HOXA9 leukemic cells in peripheral blood after 3-day tofacitinib (tofa) treatment compared with vehicle control. H, Change in WBC count before and after the treatment. I, Total WBC counts at day 35. J, Spleen weights of tofacitinib-treated vs. vehicle-treated mice at day 35. K, Ki67 staining of spleens.
Charles E. de Bock et al. Cancer Discov 2018;8:
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