Figure 4.
YKL-05-099 treatment extends survival in 2 mouse models of MLL-AF9 AML. (A) Survival curves of C57BL/6 mice transplanted with RN2 cells, followed by intraperitoneal injection of 6 mg/kg YKL-05-099 treatment once daily from day 1 after transplantation. The P value was calculated by log-rank (Mantel-Cox) test (n = 4 or 5). (B) Representative bioluminescence imaging of mice on the indicated days after transplantation. (C) Quantification of the signal in panel B. Values represent photons per second (p/s) of bioluminescent signal detection (mean ± standard error of the mean [SEM]). The P value was calculated by unpaired Student t test (n = 4 or 5). (D) Bioluminescence imaging of wild-type C57BL/6 mice that received RN2 cell transplants. YKL-05-099 was administrated twice daily from days 5 to 9 after transplantation. Representative images and quantified signal values (p/s) are shown (mean ± SEM). The P value was calculated by unpaired Student t test (n = 5). (E) The leukemia burden in bone marrow was evaluated by human CD45 flow cytometry analysis after 2 weeks of treatment with YKL-05-099 in NSGS mice receiving transplants of AML PDX model (PDX-1) cells. The mean ± standard deviation is shown (n = 4 or 5). The P value was calculated by the unpaired Student t test. (F) Survival curves of NSGS mice receiving transplants of PDX-1 AML cells. YKL-05-099 treatment (18 mg/kg, intraperitoneal injection, once daily) was initiated from day 7 after transplantation for 3 weeks. The P value was calculated by log-rank (Mantel-Cox) test (n = 8). (G-H) Flow cytometry analysis of myeloid and B- and T-cell populations in peripheral blood (G) and bone marrow (H) from C57BL/6 mice after 4 weeks of treatment with 18 mg/kg YKL-05-099. (I) Absolute number of LSK cells per femur from the mice in panel G. (J) Mouse weight measurements were performed during daily treatment with 18 mg/kg YKL-05-099 (n = 6).

YKL-05-099 treatment extends survival in 2 mouse models of MLL-AF9 AML. (A) Survival curves of C57BL/6 mice transplanted with RN2 cells, followed by intraperitoneal injection of 6 mg/kg YKL-05-099 treatment once daily from day 1 after transplantation. The P value was calculated by log-rank (Mantel-Cox) test (n = 4 or 5). (B) Representative bioluminescence imaging of mice on the indicated days after transplantation. (C) Quantification of the signal in panel B. Values represent photons per second (p/s) of bioluminescent signal detection (mean ± standard error of the mean [SEM]). The P value was calculated by unpaired Student t test (n = 4 or 5). (D) Bioluminescence imaging of wild-type C57BL/6 mice that received RN2 cell transplants. YKL-05-099 was administrated twice daily from days 5 to 9 after transplantation. Representative images and quantified signal values (p/s) are shown (mean ± SEM). The P value was calculated by unpaired Student t test (n = 5). (E) The leukemia burden in bone marrow was evaluated by human CD45 flow cytometry analysis after 2 weeks of treatment with YKL-05-099 in NSGS mice receiving transplants of AML PDX model (PDX-1) cells. The mean ± standard deviation is shown (n = 4 or 5). The P value was calculated by the unpaired Student t test. (F) Survival curves of NSGS mice receiving transplants of PDX-1 AML cells. YKL-05-099 treatment (18 mg/kg, intraperitoneal injection, once daily) was initiated from day 7 after transplantation for 3 weeks. The P value was calculated by log-rank (Mantel-Cox) test (n = 8). (G-H) Flow cytometry analysis of myeloid and B- and T-cell populations in peripheral blood (G) and bone marrow (H) from C57BL/6 mice after 4 weeks of treatment with 18 mg/kg YKL-05-099. (I) Absolute number of LSK cells per femur from the mice in panel G. (J) Mouse weight measurements were performed during daily treatment with 18 mg/kg YKL-05-099 (n = 6).

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