Isolation and Characterization of a Murine P388 Leukemia Line Resistant to Clofarabine.

A murine P388 leukemia line fully resistant to clofarabine was obtained after only two courses of intraperitoneal treatment (three times a day for nine consecutive days). The resistance was stable for at least 13 weeks without treatment. The subline was as sensitive to 5-fluorouracil, methotrexate, cyclophosphamide, cisplatin, melphalan, BCNU, doxorubicin, etoposide, irinotecan, vincristine, and docetaxel as was the parental P388/0 line but was cross-resistant to five antimetabolites [palmO-ara-C, 4′-thio-ara-C, fludarabine phosphate, cladribine, and gemcitabine—all of which require deoxycytidine kinase for activation] and paclitaxel. The subline had less than 1% of the deoxycytidine kinase activity in comparison to P388/0. [ABSTRACT FROM AUTHOR]