Figure 7.
Myeloid cell depletion reduces T-ALL burden in the CNS and supplements MTX therapy to improve in vivo survival. (A-B) Representative flow cytometry plots (A) and quantification (B) of T-ALL burden in the CNS of leukemic mice treated with PBS vehicle control (left) or Clodlip (right). Bars depict the mean + SEM of cumulative data from 5 experiments, with distinct color-coded primary LMO2 T-ALL stocks; symbols represent individual mice. (C) Experimental schematic depicting the dosing schedule for MTX treatment after LMO2 T-ALL engraftment. (D) Leukemia burden in the CNS, spleen, and blood was assessed 2 days after the second injection of MTX vs vehicle control (PBS; “control”). (E) Composition of the myeloid compartment in the CNS of mice 48 hours after receiving MTX or PBS vehicle control treatment or in mice with T-ALL that “relapsed” after MTX treatment, as indicated in panel C. Bars depict the mean + SEM of cumulative data from 6 mice, each with a color-coded unique primary T-ALL stock. (F) Quantification of viable T-ALL cells from the CNS of relapsed mice 6 to 7 days after culture in the presence or absence of myeloid cells from the CNS, normalized to “T-ALL” alone. Bars depict the mean + SEM of cumulative data from 3 experiments with distinct color-coded primary LMO2 T-ALL cells; symbols represent individual mice. (G) Experimental schematic depicting the dosing schedule for “control,” “Clodlip,” “MTX,” and combination Clodlip plus MTX therapy (“Both”). (H) Kaplan-Meier survival curves of mice from 3 independent experiments in which distinct primary LMO2 T-ALL stocks were engrafted into littermates, with a total of 6 mice per treatment group. Statistical significance was determined using unpaired Student t test (Mann-Whitney U) in panels B,D-F or log-rank test in panel H (∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001).

Myeloid cell depletion reduces T-ALL burden in the CNS and supplements MTX therapy to improve in vivo survival. (A-B) Representative flow cytometry plots (A) and quantification (B) of T-ALL burden in the CNS of leukemic mice treated with PBS vehicle control (left) or Clodlip (right). Bars depict the mean + SEM of cumulative data from 5 experiments, with distinct color-coded primary LMO2 T-ALL stocks; symbols represent individual mice. (C) Experimental schematic depicting the dosing schedule for MTX treatment after LMO2 T-ALL engraftment. (D) Leukemia burden in the CNS, spleen, and blood was assessed 2 days after the second injection of MTX vs vehicle control (PBS; “control”). (E) Composition of the myeloid compartment in the CNS of mice 48 hours after receiving MTX or PBS vehicle control treatment or in mice with T-ALL that “relapsed” after MTX treatment, as indicated in panel C. Bars depict the mean + SEM of cumulative data from 6 mice, each with a color-coded unique primary T-ALL stock. (F) Quantification of viable T-ALL cells from the CNS of relapsed mice 6 to 7 days after culture in the presence or absence of myeloid cells from the CNS, normalized to “T-ALL” alone. Bars depict the mean + SEM of cumulative data from 3 experiments with distinct color-coded primary LMO2 T-ALL cells; symbols represent individual mice. (G) Experimental schematic depicting the dosing schedule for “control,” “Clodlip,” “MTX,” and combination Clodlip plus MTX therapy (“Both”). (H) Kaplan-Meier survival curves of mice from 3 independent experiments in which distinct primary LMO2 T-ALL stocks were engrafted into littermates, with a total of 6 mice per treatment group. Statistical significance was determined using unpaired Student t test (Mann-Whitney U) in panels B,D-F or log-rank test in panel H (∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001).

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