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 5
ICSBP protects from AML in a tyrosine phosphorylation–dependent manner. Development of leukemia in WT, ICSBP^+/–, and ICSBP^–/– mice or mice transplanted with ICSBP^–/– bone marrow that was transduced with vectors to express WT or Y-mut ICSBP or vector control was monitored. Peripheral blood counts with leukocyte differential were determined every 4 weeks. Mice with greater than 20% myeloid blasts were considered to have AML. The percentage of mice without leukemia was plotted as a function of age. (A) AML developed by 6 months in ICSBP^–/– mice. Fifty percent of ICSBP^–/– mice had AML by 16 weeks and 100% by 24 weeks. In contrast, only a few ICSBP^+/– mice exhibited 20% blasts in the circulation by 24 weeks. (B) Expression of ICSBP, but not Y-mut ICSBP, delayed development of AML in mice transplanted with ICSBP^–/– bone marrow. Fifty percent of mice transplanted with control vector or Y-mut ICSBP expression vector–transduced ICSBP^–/– bone marrow developed AML between 16 and 20 weeks. Two mice transplanted with ICSBP expression vector–transduced ICSBP^–/– bone marrow developed AML during the observation period. (C) Myeloid blasts in transplanted mice. Peripheral smears of myeloid blasts from mice transplanted with ICSBP^–/– bone marrow that was transduced with vectors to express ICSBP or Y-mut ICSBP or control vector were compared with blasts from mice transplanted with ICSBP^+/– bone marrow that had been transduced with a vector to express E76K SHP2. The blasts were morphologically similar. Original magnification, ×40.