FLT3-ITD induced T-ALL in BMT mice using RSK2 KO BM cells, phenotypically distinct from the myeloproliferative neoplasm induced by FLT3-ITD using WT BM cells. (A) Kaplan-Meier survival plot of mice receiving either WT or RSK2 KO BM cells retrovirally transduced by FLT3-ITD. All BMT mice in the WT group (n = 9) developed an aggressive and fatal myeloproliferative neoplasm. In contrast, 6 of 10 mice in the group receiving RSK2 KO BM cells transformed by FLT3-ITD developed T-ALL characterized by thymic enlargement, with a significantly longer latency, while 4 mice in this group did not develop any discernable disease by the experimental end point (180 day). The statistical significance for survival was assessed by log-rank. (B) Analyses of mice transplanted with either WT or RSK2 KO BM cells expressing FLT3-ITD. (C) Flow cytometric analysis demonstrates an expansion of Gr-1/Mac-1 double-positive mature myeloid cells in spleen and BM consistent with a myeloproliferative neoplasm in a representative BMT mouse receiving WT BM cells expressing FLT3-ITD (top left), whereas such myeloid expansion was absent in the representative FLT3-ITD mouse receiving RSK2 KO BM cells (top right). Instead, an expansion of CD4/CD8 double-positive T cells in spleen and thymus consistent with T-ALL was detected in the representative FLT3-ITD BMT mouse receiving RSK2 KO BM cells (bottom right), compared with the FLT3-ITD mouse receiving WT BM cells (bottom left). (D) Tissue sections of spleen, BM, and liver demonstrate evidence of a marked myeloproliferative neoplasm with an expansion of maturing myeloid cells observed in the representative FLT3-ITD BMT mouse receiving WT cells, and a T-ALL disease in the FLT3 mouse receiving RSK2 KO BM cells. Magnifications are as indicated (H&E).