Fig. 4: TXNIP compromises imatinib-resistant CML cell growth and CML transformation.

A Schematic strategy of evaluation of the in vivo effect of TXNIP overexpression on CML transformation. B Kaplan–Meier-style survival curves for recipients of BCR-ABL-TXNIP-GFP or BCR-ABL-GFP transduced BM cells from C57BL/6 (n = 12) mice. C Apoptosis of BCR-ABL or MIGR1 (CTRL) transduced normal CD34⁺ cells with or without TXNIP overexpression. The double-transduced CD34⁺ cells were sorted and then analyzed for annexin V + cells after 48 h of culture. D, E Analysis of total cell numbers (D) and CFC formation (E) of BCR-ABL-TXNIP-GFP or BCR-ABL-GFP transduced normal CD34⁺ cells. F The cell viability was determined in K562, K562G, and K562R cells following indicated doses of imatinib treatment for 72 h, and normalized to the control group. G TXNIP and c-Myc expressions in K562, K562G, and K562R cells. H TXNIP and c-Myc expressions in TXNIP overexpressed K562G and K562R cells. I–L In TXNIP overexpressed K562G and K562R cells, the cell viabilities were determined by CCK8 (I) and Edu staining (J) assay. The CFC formation (K) and apoptosis (L) were analyzed, respectively. M Survival curves of mice receiving xenografted CML cells. K562G or K562R cells with or without TXNIP overexpression were inoculated into nude mice. Mice were euthanized when the tumor volume reached 1000 mm³. N The human primary CML CD34⁺ cells were infected with TXNIP lentivirus, and then injected into sublethally irradiated (300 cGy) NSI mice. After 12 weeks, human multilineage engraftment was analyzed by flow cytometry. O, P The percentage (O) and the absolute number (P) of human CD45⁺ cells engrafted in the BM after transplantation of human CML CD34⁺ cells (1 × 10⁶ cells/mouse) for 12 weeks. Q The proportion of human CD45⁺ cells engrafted in the spleen at 12 weeks. R The CFC formation after TXNIP overexpression. ***P < 0.001. **P < 0.01.