Fig. 3: Suppression of TXNIP confers CML cell growth and counteracts imatinib sensitivity.

A Schematic strategy of evaluation of the in vivo effect of TXNIP knockout on CML transformation. B Kaplan–Meier-style survival curves for recipients of BCR-ABL-Cre-GFP or BCR-ABL-GFP transduced BM cells from TXNIP^fl/fl (n = 10) mice. C Apoptosis of BCR-ABL or MIGR1 (CTRL) transduced normal CD34⁺ cells with or without Cre overexpression in the presence of 2 μM imatinib. 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 colony-forming cell (CFC) formation (E) of BCR-ABL-Cre-GFP or BCR-ABL-GFP transduced normal CD34⁺ cells with 2 μM imatinib treatment. F The indicated protein levels were determined by western blot in K562 and KCL22 cells after TXNIP knockdown. G The cell viabilities of K562 and KCL22 cells were determined after TXNIP knockdown in indicated days. H The cell viability was determined in K562 and KCL22 cells following indicated doses of imatinib treatment for 72 h, and normalized to the control group. I Edu incorporation assay was performed for cell viability determination in K562 and KCL22 cells after TXNIP knockdown with or without 2 μM imatinib treatment. J K562 and KCL22 cells were plated in methylcellulose-containing medium after TXNIP knockdown, with or without imatinib treatment. The CFC were scored after 1 week. K Apoptosis was analyzed 48 h after imatinib treatment. L Representative bioluminescence imaging photographs of tumor burden in nude mice (n = 6) 24 days after the subcutaneous injection of indicated cells. sh#2: shTXNIP#2. M The Tumor size was measured and tumor volume was calculated by the formula (width² × length × 0.5). IM: imatinib. ***P < 0.001. **P < 0.01.