ALL-TRANS-RETINOIC ACID IN HEMATOLOGICAL MALIGNANCIES - AN UPDATE

Background and Objective. During the past ten years, the study of reti noids has undergone a total transformation. The Italian Society of Exp erimental Hematology decided to discuss these advances at a meeting in Florence on April 18, 1996. Information sources. The material examine d in the present review includes articles and abstracts published in j ournals covered by the Science Citation Index(R) and Medline(R). In ad dition, all the authors of the present article have been actively work ing in the field of retinoids and have contributed several papers. Sum maries of their oral presentations at the Florence meeting are reporte d in the Appendix to this review article. State of Art and Perspective s. One of the most important advances has been the elucidation of new molecular mechanisms of control of gene expression by retinoids. A num ber of new retinoids have been synthesized by chemists, some of which are being screened for potential clinical use, and a few have already had a tremendous impact on clinical practice. The most important achie vements have been obtained in acute promyelocytic leukemia. In 1988 a Chinese group working in Shanghai showed that using all-trans retinoic acid (ATRA) alone 94% of acute promyelocytic leukemic patients obtain ed complete remission through differentiation of the leukemic clone. T his result transformed a dream into reality and allowed researchers to move from laboratory experience to clinical applications of this diff erentiating therapy. Expanding the spectrum of hematological malignanc ies that may respond to ATRA remains a challenge; however, several res ults show some activity of retinoids alone or in combination with othe r drugs in juvenile chronic myeloid leukemia (CML), myelodysplastic sy ndrome, cutaneous T-cell lymphoma and CML. Particularly interesting ar e the studies that explored the potential clinical synergism of ATRA-b ased combination therapies with growth factors, other differentiating agents such as vitamin D3, immunomodulators like interferons, or chemo therapeutic agents, in particular Ara-C, all of which show promising i n vitro effects when used in combination with retinoids. (C) 1997, Fer rata Storti Foundation.