High incidence of leukemia in large animals after stem cell gene therapy with a HOXB4-expressing retroviral vector
J. Clin. Invest. Xiao-Bing Zhang, et al. 118:1502 doi:10.1172/JCI34371 [
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Figure 3HOXB4 overexpression contributes to leukemogenesis. (
A) Western blot analysis showed strong HOXB4 expression in marrow cells from leukemic animals. HOXB4-overexpressing dog cells in ex vivo culture were used as a positive control and marrow cells from normal dog as a negative control. (
B) Knockdown of
PRDM16 or
MYB decreased the proliferation rate of the dog G374 leukemic cells. (
C)
HOXB4 knockdown in the leukemic cell line induced cell differentiation and (
D) abolished cell proliferation. The stem cell marker CD34 and mature granulocyte marker Dm5 were used to evaluate cell differentiation. The leukemic cell line was cultured in medium supplemented with cSCF, thrombopoietin, and Flt3-L each at 100 ng/ml.
