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 3
ICSBP tyrosine phosphorylation regulated apoptosis in differentiating myeloid cells. (A) Regulation of apoptosis by ICSBP is tyrosine phosphorylation dependent. Myeloid progenitors were isolated from the bone marrow of ICSBP^–/– or WT mice and cultured in GM-CSF and IL-3. ICSBP^–/– cells were transduced with a retroviral vector to express ICSBP, Y-mut ICSBP, or vector control. WT cells were transduced with vector control. Apoptosis was determined after 48 hours in a dose titration of IL-3 by annexin V staining. In comparison to WT cells, ICSBP^–/– cells that had been transduced with empty vector or Y-mut ICSBP expression vector exhibited significantly less apoptosis at the lowest IL-3 doses (*P < 0.02). Apoptosis in ICSBP^–/– cells transduced with a vector to express WT ICSBP was not significantly different from that in WT cells. (B) WT and Y-mut ICSBP are equivalently expressed in myeloid progenitors. Lysate proteins from the transduced ICSBP^–/– cells, discussed above, were analyzed for ICSBP expression by Western blotting. Blots were serially probed with antibodies against ICSBP and actin (as a loading control).