Figure 4
Figure 4. Effect of CD38 antibody in NOD/SCID/β2m−/− and NOD/SCID/IL2rγ−/− mice. AML cells were incubated with either isotype control or test antibody and transplanted into mice. (A) A total of 5.5 × 106 AML cells (sample 3) were transplanted into NOD/SCID/β2m−/− mice. Both the HIT2 and AT13/5 clones of anti-CD38 antibody abolished engraftment of AML at 6 weeks. Blasts from sample 3 express CD33 and CD13. A total of 7.5 × 106 T-cell-deplete AML cells were transplanted into NOD/SCID/IL2rγ−/− mice from sample 4 (B) and sample 5 (C). Engraftment of both AML and normal human hematopoietic cells was noted in each mouse. The percentage of human cells with mutant NPM and wild-type (WT) NPM was determined quantitatively to assess percentage of normal and AML cells. ● and ○ represent the percentage of total bone marrow that was leukemic. ▴ and ▵ represent the percentage of bone marrow that was normal human hematopoietic cells. Note that for each mouse there is a circle and a triangle. For each AML sample, there was a significant reduction in the percentage of AML in mice receiving cells incubated with CD38 antibody (P = .001), whereas there was no significant reduction in normal hematopoietic cells from these same mice (P > .1).

Effect of CD38 antibody in NOD/SCID/β2m−/− and NOD/SCID/IL2rγ−/− mice. AML cells were incubated with either isotype control or test antibody and transplanted into mice. (A) A total of 5.5 × 106 AML cells (sample 3) were transplanted into NOD/SCID/β2m−/− mice. Both the HIT2 and AT13/5 clones of anti-CD38 antibody abolished engraftment of AML at 6 weeks. Blasts from sample 3 express CD33 and CD13. A total of 7.5 × 106 T-cell-deplete AML cells were transplanted into NOD/SCID/IL2rγ−/− mice from sample 4 (B) and sample 5 (C). Engraftment of both AML and normal human hematopoietic cells was noted in each mouse. The percentage of human cells with mutant NPM and wild-type (WT) NPM was determined quantitatively to assess percentage of normal and AML cells. ● and ○ represent the percentage of total bone marrow that was leukemic. ▴ and ▵ represent the percentage of bone marrow that was normal human hematopoietic cells. Note that for each mouse there is a circle and a triangle. For each AML sample, there was a significant reduction in the percentage of AML in mice receiving cells incubated with CD38 antibody (P = .001), whereas there was no significant reduction in normal hematopoietic cells from these same mice (P > .1).

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