Figure 5.

Copanlisib decreases CNS invasion, inhibits BM disease progression, and improves response to chemotherapy in leukemic mice. (A) Schematic of copanlisib treatment of leukemic mice. (B) Kaplan-Meier survival curve of RCH-ACV engrafted SCID mice treated with copanlisib vs. vehicle. Two-sided log rank Mantel-Cox test, vehicle: n = 6 mice, copanlisib: n = 4 mice; p = 0.0045. (C) Incidence of hind-limb paralysis at clinical endpoint in RCH-ACV engrafted mice. (D and E) Disease burden in the BM (percentage of CD19⁺ ALL cells) and in the CNS (number of CD19⁺ ALL cells) of vehicle- and copanlisib-treated RCH-ACV engrafted mice euthanized at matched time points. Paired two-sided Student’s t-test, n 5 mice per treatment group; p < 0.01, p < 0.001. (F) Incidence of hind-limb paralysis in RCH-ACV engrafted mice at paired=analysis. (G and H) Disease burden in the BM (percentage of CD10⁺ ALL cells) and in the CNS (number of CD10⁺ ALL cells) of vehicle- and copanlisib-treated Nalm-6 engrafted mice euthanized at matched time points. Paired two-sided Student’s t-test, n = 4 mice per treatment group; p < 0.05. (I) Incidence of hind-limb paralysis in Nalm-6 engrafted mice at paired analysis. (J) RCH-ACV ALL cells in subarachnoid space (dashed line) of the spinal cord (SC) at paired analysis. Representative histologic sections of the vertebrae are shown. H&E, hematoxylin and eosin. n = 5 mice per treatment group.