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Differentiation Therapy of Acute Promyelocytic Leukemia with Tretinoin (All-trans-Retinoic Acid)
Open accessAbstract
BACKGROUND AND METHODS: Patients with acute promyelocytic leukemia have a characteristic (15;17) translocation, with a breakpoint on chromosome 17 in the region of the retinoic acid receptor-alpha (RAR-alpha). Since this receptor has been shown to be involved with growth and differentiation of myeloid cells in vitro, and since recent clinical studies have reported that tretinoin (all-trans-retinoic acid) induces complete remission in patients with acute promyelocytic leukemia we studied the effects of tretinoin on cellular maturation and molecular abnormalities in patients undergoing the induction of remission with this agent. RESULTS: Eleven patients with acute promyelocytic leukemia were treated with tretinoin administered orally at a dose of 45 mg per square meter of body-surface area per day. Nine of the 11 patients entered complete remission. In two patients, complete remission was preceded by striking leukocytosis that then resolved despite continued drug treatment. Serial studies of cellular morphologic features, cell-surface immunophenotypic analysis, and fluorescence in situ hybridization with a chromosome 17 probe revealed that clinical response was associated with maturation of the leukemic clone. All patients who responded to treatment who were tested by Northern blot analysis had expression of aberrant RAR-alpha. As patients entered complete remission, the expression of the abnormal RAR-alpha message decreased markedly; however, it was still detectable in several patients after complete morphologic and cytogenetic remission had been achieved. CONCLUSIONS: Tretinoin is a safe and highly effective agent for inducing complete remission in patients with acute promyelocytic leukemia. Clinical response to this agent is associated with leukemic-cell differentiation and is linked to the expression of an aberrant RAR-alpha nuclear receptor. Molecular detection of the aberrant receptor may serve as a useful marker for residual leukemia in patients with this disease.
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Cites
A human retinoic acid receptor which belongs to the family of nuclear receptors
Petkovich, M., Brand, N. J., Krust, A., & Chambon, P. (1987) · Nature · doi:10.1038/330444a0 · Cited by 2,214
Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid
Breitman, T. R., Selonick, S. E., & Collins, S. J. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.5.2936 · Cited by 1,966
Cited by
All-trans-Retinoic Acid in Acute Promyelocytic Leukemia
Tallman, M. S., Andersen, J. W., Schiffer, C. A., Appelbaum, F. R., Feusner, J. H., Ogden, A., Shepherd, L., Willman, C., Bloomfield, C. D., Rowe, J. M., et al. (1997) · New England Journal of Medicine · doi:10.1056/nejm199710093371501 · Cited by 1,073
Warrell, R. P., He, L.-Z., Richon, V., Calleja, E., & Pandolfi, P. P. (1998) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/90.21.1621 · Cited by 502
Self-citationLazo, G., Kantarjian, H., Estey, E., Thomas, D., O'Brien, S., & Cortes, J. (2003) · Cancer · doi:10.1002/cncr.11314 · Cited by 494
Smith, M. A., Parkinson, D. R., Cheson, B. D., & Friedman, M. A. (1992) · Journal of Clinical Oncology · doi:10.1200/jco.1992.10.5.839 · Cited by 486
Cellular plasticity and the neuroendocrine phenotype in prostate cancer
Davies, A. H., Beltran, H., & Zoubeidi, A. (2018) · Nature Reviews Urology · doi:10.1038/nrurol.2018.22 · Cited by 431
Metadata
- Authors
- Warrell, R. P., Frankel, S. R., Miller, W. H., Scheinberg, D. A., Itri, L. M., Hittelman, W. N., Vyas, R., Andreeff, M., Tafuri, A., Jakubowski, A., Gabrilove, J., Gordon, M. S., & Dmitrovsky, E.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1991-05-16
- Volume
- 324
- Issue
- 20
- Pages
- 1385-1393
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2327237185
- Cited by
- 1,251
- References
- 2
- FWCI
- 32.09
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Warrell, R. P., Frankel, S. R., Miller, W. H., Scheinberg, D. A., Itri, L. M., Hittelman, W. N., Vyas, R., Andreeff, M., Tafuri, A., Jakubowski, A., Gabrilove, J., Gordon, M. S., & Dmitrovsky, E. (1991). Differentiation Therapy of Acute Promyelocytic Leukemia with Tretinoin (All-trans-Retinoic Acid). New England Journal of Medicine. https://doi.org/10.1056/nejm199105163242002
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