Transcriptomic differences in cabozantinib-resisant AML cells.

Cabozantinib is a type II tyrosine kinase inhibitor (TKI), which is approved by FDA for treating several solid tumors including advanced/progressive metastatic medullar thyroid cancer, advanced renal cell carcinoma, and advanced and progressive hepatocellular carcinoma. Moreover, we and others revealed its cytotoxicity on FLT3-ITD, KIT-driven t(8;21) AML cells, and its efficacy on promoting erythroid differentiation of leukemic cell line K562. A clinical trial report also suggested that cabozantinib is well tolerated in FLT3-ITD AML patients. While those findings highlighted the feasibility of cabozantinib targeting specific AML subtypes, it is unclear whether cabozantinib treatment arises resistance in cancer cells. To identify the mechanism and transcriptomic change of cabozantinib resistance, we established drug-resistant cell lines by culturing Molm13 and MV4-11 leukemic cell lines in increasing drug concentrations. Overall design: The cabozantinib-resistant cells (Molm13-XR and MV4-11-XR cells) were derived by culturing the parental cells in low-concentration cabozantinib and escalating the dose once the cells were recovered.