Constitutive activation of SHP2 in mice cooperates with ICSBP deficiency to accelerate progression to acute myeloid leukemia
J. Clin. Invest. Iwona Konieczna, et al. 118:853 doi:10.1172/JCI33742 [Go to this article.]

Figure 4
ICSBP tumor suppression required tyrosine phosphorylation. WT irradiated mice were transplanted with ICSBP^–/– bone marrow that had been transduced with a retroviral vector to express ICSBP or Y-mut ICSBP, or control vector. Peripheral blood counts were determined every 4 weeks for 28 weeks. (A) MPD and AML developed in mice transplanted with control vector–transduced ICSBP^–/– bone marrow. Control mice rapidly developed leukocytosis with neutrophilia. Numbers of myeloid blasts were equivalent to PMN numbers by 12 weeks and continued to increase throughout the observation period. (B) MPD and AML were delayed in mice transplanted with ICSBP^–/– bone marrow that had been transduced with an ICSBP expression vector. Total leukocytes were significantly reduced in these mice in comparison to mice transplanted with control or Y-mut ICSBP–expressing ICSBP^–/– bone marrow (*P < 0.0001). ICSBP reconstitution resulted in a normal, lymphocyte-dominant differential blood counts. Significantly fewer myeloid blasts were present in the circulation of these mice in comparison to the other 2 groups (**P < 0.001). (C) MPD and AML developed in mice transplanted with ICSBP^–/– bone marrow that had been transduced with a vector to express Y-mut ICSBP. These mice developed leukocytosis with neutrophilia and increasing myeloid blasts in a manner that was not significantly different than mice transplanted with control ICSBP^–/– bone marrow. (D) Splenomegaly was reduced in mice transplanted with ICSBP^–/– bone marrow that was transduced with an ICSBP expression vector. Spleens harvested from mice 24 weeks after transplantation were significantly smaller in mice with ICSBP-reconstituted ICSBP^–/– bone marrow in comparison to the other 2 groups.