Figure 4.
Lenalidomide toxicity is enhanced by haploinsufficiency of Csnk1a1. (A) Schematic for the Csnk1a1 competitive transplant experiment. After hematopoietic reconstitution, chimeric transplants containing 50% Csnk1a1−/+, CrbnI391V (mutant, CD45.2), and 50% CrbnI391V (WT, CD45.1) were treated with vehicle (DMSO), lenalidomide 50 mg/kg BID, pomalidomide 20 mg/kg BID, or iberdomide 20 mg/kg BID. (B) Total peripheral white blood cell count was determined using fluorescence-assisted cell sorting. (C) PB was collected weekly and chimerism was measured using fluorescence-assisted cell sorting. (D) BM was harvested and chimerism measured within each of the following cellular compartments: LSK, LT-HSC (LSK, CD150+, and CD48−), ST-HSC (LSK, CD150−, and CD48−), MPP (LSK, CD150−, and CD48+), CMP (LK, CD16/32−, and CD34+), and GMP (LK, CD16/32−, and CD34−). Shown is the mean ± the standard error of the mean (n = 8-10 mice per group). ∗∗∗P < .0001, one-way ANOVA.

Lenalidomide toxicity is enhanced by haploinsufficiency of Csnk1a1. (A) Schematic for the Csnk1a1 competitive transplant experiment. After hematopoietic reconstitution, chimeric transplants containing 50% Csnk1a1−/+, CrbnI391V (mutant, CD45.2), and 50% CrbnI391V (WT, CD45.1) were treated with vehicle (DMSO), lenalidomide 50 mg/kg BID, pomalidomide 20 mg/kg BID, or iberdomide 20 mg/kg BID. (B) Total peripheral white blood cell count was determined using fluorescence-assisted cell sorting. (C) PB was collected weekly and chimerism was measured using fluorescence-assisted cell sorting. (D) BM was harvested and chimerism measured within each of the following cellular compartments: LSK, LT-HSC (LSK, CD150+, and CD48−), ST-HSC (LSK, CD150−, and CD48−), MPP (LSK, CD150−, and CD48+), CMP (LK, CD16/32−, and CD34+), and GMP (LK, CD16/32−, and CD34−). Shown is the mean ± the standard error of the mean (n = 8-10 mice per group). ∗∗∗P < .0001, one-way ANOVA.

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