Microtubule Changes in Hematologic Malignant Cells Treated with Paclitaxel and Comparison with Vincristine Cytotoxicity

Abstract

ABSTRACT Using immunofluorescence microscopy with an anti-alpha tubulin monoclonal antibody, we examined the microtubule changes induced by paclitaxel in pathologic cells from 38 hematologic malignancies, and compared the morphologic and cytotoxic changes with those induced by vincristine in vitro. Malignant cells cultured without paclitaxel or vincristine (controls) showed well-developed microtubules radiating from a microtubule organizing center (MTOC). Malignant cells cultured with paclitaxel showed bundling of microtubules and those cultured with vincristine showed crystal formation of the microtubules. In 28 lymphoid malignancies, the difference in the percentage of cells showing microtubular changes with paclitaxel and vincristine was significant (paired t test) after 2h P<0.01, after 4h P<0.05, and after 20h P<0.05. As paclitaxel is not in clinical use for the treatment of hematologic malignancies in Japan, no clinical material was available. In 6 out of 9 patients with lymphoid malignancies with a previous history of combined chemotherapy including vincristine, paclitaxel produced microtubular changes in a higher percentage of cells than did vincristine. In 10 myeloid malignancies, the percentages of the cells with microtubular changes induced by paclitaxel was also higher than those induced by vincristine (P<0.05 in 2 h, P<0.01 in 4h, and P<0.05 in 20h). Although the number of studied cases was small, this suggests that paclitaxel is as effective as vincristine in certain hematologic malignancies. As microtubular changes induced by paclitaxel and vincristine are easy to assess, the study of microtubular changes induced in vitro by antimicrotubular agents may prove useful in predicting the chemotherapeutic effect in vivo of these agents.