All-trans retinoic acid in hematological malignancies, an update. GER (Gruppo Ematologico Retinoidi).
OBJECTIVE
During the past ten years, the study of retinoids has undergone a total transformation. The Italian Society of Experimental Hematology decided to discuss these advances at a meeting in Florence on April 18, 1996.


METHODS
The material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline. In addition, all the authors of the present article have been actively working in the field of retinoids and have contributed several papers. Summaries of their oral presentations at the Florence meeting are reported in the Appendix to this review article.


CONCLUSIONS
One of the most important advances has been the elucidation of new molecular mechanisms of control of gene expression by retinoids. A number 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 achievements 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 obtained complete remission through differentiation of the leukemic clone. This result transformed a dream into reality and allowed researchers to move from laboratory experience to clinical applications of this differentiating therapy. Expanding the spectrum of hematological malignancies that may respond to ATRA remains a challenge; however, several results show some activity of retinoids alone or in combination with other drugs in juvenile chronic myeloid leukemia (CML), myelodysplastic syndrome, cutaneous T-cell lymphoma and CML. Particularly interesting are the studies that explored the potential clinical synergism of ATRA-based combination therapies with growth factors, other differentiating agents such as vitamin D3, immunomodulators like interferons, or chemotherapeutic agents, in particular Ara-C, all of which show promising in vitro effects when used in combination with retinoids.
Sacchi
S
S
Dipartimento di Scienze Mediche, Oncologiche e Radiologiche, Università di Modena, Italy. ssacchi@unimo.it
Russo
D
D
Avvisati
G
G
Dastoli
G
G
Lazzarino
M
M
Pelicci
P G
PG
Bonora
M R
MR
Visani
G
G
Grassi
C
C
Iacona
I
I
Luzzi
L
L
Vanzanelli
P
P
D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001711:Biotransformation; D002454:Cell Differentiation / Q000187:drug effects; D002648:Child; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D005786:Gene Expression Regulation / Q000187:drug effects; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008957:Models, Genetic; D014411:Neoplastic Stem Cells / Q000187:drug effects; D011559:Pseudotumor Cerebri / Q000139:chemically induced; D018168:Receptors, Retinoic Acid / Q000187:drug effects; D012074:Remission Induction; D012120:Respiration Disorders / Q000139:chemically induced; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D018168:Receptors, Retinoic Acid; D014212:Tretinoin