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. 2013 Apr 12;27(12):2301–2310. doi: 10.1038/leu.2013.83

Figure 7.

Figure 7

Depletion of KDELR1 reduces transforming capacity. (a) Clonal growth of MV4-11 cells expressing shKDELR1 (hK02) and shRNA control cells were subjected to colony formation assays in methylcellulose in RPMI medium with 10% FCS. Number of colonies per well were counted after 8 days. Means of normalized values for three separate experiments ±s.d., significance tested by t-test. (b) Knockdown of KDELR1 enhances survival in mice transplanted with 32D FLT3-ITD cells. Kaplan–Meier plot of survival of mice injected with 32D FLT3-ITD cells expressing indicated shRNAs. Development of a leukemia-like disease was analyzed (n=11). For comparison, 32D FLT3-ITD cells expressing a nontargeting shRNA (n=10) were injected. The percentage of surviving mice (y-axis) is plotted with respect to time in days (x-axis). Statistic significance of different survival of mice was P<0.002 (Gehan–Breslow Test). (c) Liver from naive C3H mice (left panel) shows a regular architecture of lobuli, portal field and terminal hepatic venule (black arrow). Mice injected with 32D muFLT3-ITD control shRNA cells (middle panel) exhibit pronounced destruction in liver and spleen with moderate-to-severe hepatomegaly with massive diffuse and nodular leukemic infiltrates (black arrow), focal hepatocellular damage, dilated sinusoids, focal fatty degeneration of hepatocytes (black arrowhead) and massive intravascular leukemic infiltrates in portal and terminal hepatic venule with focal vascular occlusions (black/white arrow). (d) Severe splenomegaly with massive diffuse leukemic infiltrates in red pulp and moderate-to-severe atrophy in white pulp (black arrowhead). Mice injected with 32D muFLT3-ITD control shRNA cells with KDELR1 knockdown (right panel) exhibit a less pronounced pathology, that is, moderate hepato- and splenomegaly, leukemic infiltrates located inside dilated sinusoids in liver (black arrow) as well as diffuse leukemic infiltrates in red pulp (black arrow) and only a moderate atrophy of white pulp (black/white arrow) within the spleen.