ABSTRACT. Blood cytopenia is a common feature in HIV infection, occurring in up to 70% of patients with AIDS. Since at present it is not clear to what extent this is intrinsic to HIV infection or due to opportunistic infections and antiretroviral agents we have investigated the long-term effects of conventional and new antiviral drugs on the bone marrow of normal and immunodeficient mice. The results show that azidothymidine (AZT), dideoxycytidine (DDC) and dideoxycytidine 5'-triphosphate (DDCTP) alone or in combination are all effective in inhibiting the expression of the retroviral protein Pr60gag in bone marrow cells. However, DDCTP was the most effective in preventing bone marrow cytopenia. Combined treatments of AZT plus DDCTP result in a reduction in erythroid precursors compared to that resulting from DDCTP administration, while DDC plus DDCTP results in a differential cell count similar to that found in uninfected mice. Thus, the bone marrow in murine AIDS may prove useful as a model for therapy of retroviral infections and for treating blood cytopenias.

Keywords: Bone marrow; cytopenia; murine AIDS; AZT; DDC; DDCTP

Reprint requests to:  Dr. Giorgio Brandi, Istituto di Igiene, Universit… degli Studi di Urbino, Via S. Chiara, 27, 61029 Urbino, Italy. Phone: 39-722-4717; Fax: 39-722-4717 (or 39-722-320188).

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.

Keywords: microtubules, fluorescence microscopy, hematologic malignancy, Paclitaxel-Vincristine

Reprint requests to:  Dr. Y. Hirose, Division of Hematology and Immunology, Department of Internal Medicine, Kanazawa Medical University, Daigaku 1-1, Uchinada-machi, Kahoku-gun, Ishikawa Prefecture 920-02, Japan, phone 0762-86-3511 ext. 3543; fax 0762-86-5613.