Figure 4.
Sequestration of BIM to upregulated BCL-XL belongs to hallmarks of acquired VEN resistance. (A-E) Western blot analysis of selected BCL2 family proteins (MCL1, BCL-XL, BCL2, BAK, and BIM) in cell lysates isolated from the subcutaneous cell line–based xenograft (CDX) tumors (HBL-2, MAVER-1, and UPF1H), and subcutaneous patient-derived xenograft (PDX) tumors (VFN-M1 and VFN-ALL6) obtained from the untreated animals (CTRL) and from the animals with acquired VEN resistance. (F-H) IP of the selected CDX or PDX tumors with anti-BIM antibody and subsequent detection of BCL-XL and BCL2 bound on BIM; 1 CDX model (UPF1H) and 2 PDX models (VFN-M1 and VFN-ALL6) were analyzed; the mice were euthanized and tumors analyzed 24 hours after the last dose of VEN.

Sequestration of BIM to upregulated BCL-XL belongs to hallmarks of acquired VEN resistance. (A-E) Western blot analysis of selected BCL2 family proteins (MCL1, BCL-XL, BCL2, BAK, and BIM) in cell lysates isolated from the subcutaneous cell line–based xenograft (CDX) tumors (HBL-2, MAVER-1, and UPF1H), and subcutaneous patient-derived xenograft (PDX) tumors (VFN-M1 and VFN-ALL6) obtained from the untreated animals (CTRL) and from the animals with acquired VEN resistance. (F-H) IP of the selected CDX or PDX tumors with anti-BIM antibody and subsequent detection of BCL-XL and BCL2 bound on BIM; 1 CDX model (UPF1H) and 2 PDX models (VFN-M1 and VFN-ALL6) were analyzed; the mice were euthanized and tumors analyzed 24 hours after the last dose of VEN.

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