Figure 5.

Suppression of Kdm4c Inhibits Hematopoietic Transformation and Leukemogenesis

(A) RTTA showing the effect of two different Kdm4c shRNAs on leukemic transformation.

(B) FACS analysis showing the effect of Kdm4c knockdown on Mac1 expression.

(C) Cell-cycle analysis after Kdm4c knockdown.

(D) Apoptosis analysis after Kdm4c knockdown.

(E) Murine leukemia cells were transduced with the control or shKdm4c lentivirus and transplanted into syngeneic mice. Bone marrows were harvested after 72 hr and the percentage of donor cells was determined by FACS.

(F) Kaplan-Meier survival analysis on the effect of Kdm4c knockdown (shKdm4c#1) on leukemogenesis (log-rank test p < 0.0001). Median disease latency: control MLL-AF9, 31 days; MLL-GAS7, 37 days; MOZ-TIF2, 33 days; shKdm4c, undefined.

(G) Effect of Kdm4c knockdown on the colony-forming ability of HSPC. Scale bar represents 0.5 cm.

(H) CFU assay showing the effect of Kdm4c knockdown on the types and number of myeloid colonies derived from HSPC. Scale bar represents 0.5 cm.

(I) FACS analysis of HSPC engraftment using CD45.1 marker to detect the donor cell populations in peripheral blood 6 weeks after transplantation (n = 5).

(J) FACS analysis of the effect of Kdm4c knockdown on both myeloid (left) and lymphoid populations (right) in peripheral blood (n = 5).

All data shown are mean and SD (n = 3) unless otherwise specified. See also Figure S5.