The advent of retinoic acid (RA) in the treatment of acute promyelocytic leukemia (APL) has led to a high frequency of short-lasting complete remissions (CR). We studied the response to RA by molecularly analyzing the RA receptor alpha (RAR alpha) locus, which has recently been shown to be rearranged in all APLs. Southern blot analysis demonstrated that the RAR alpha rearrangements persisted in the APL samples containing maturing myeloid cells 2 to 3 weeks after the start of RA treatment, but disappeared after 5 to 8 weeks, when the patients achieved CR. Our investigations provide clear evidence that CR occurs at molecular level and that there is reconstitution of an apparently normal, nonclonal hematopoiesis. Further, it shows that RA acts by triggering differentiation rather than by exerting a cytotoxic effect on the leukemic clone.

Lo Coco, F., Avvisati, G., Diverio, D., Petti, M.c., Alcalay, M., Pandolfi, P.p., et al. (1991). Molecular evaluation of response to all-trans-retinoic acid therapy in patients with acute promyelocytic leukemia. BLOOD, 77(8), 1657-1659.

Molecular evaluation of response to all-trans-retinoic acid therapy in patients with acute promyelocytic leukemia

LO COCO, FRANCESCO;
1991-04-15

Abstract

The advent of retinoic acid (RA) in the treatment of acute promyelocytic leukemia (APL) has led to a high frequency of short-lasting complete remissions (CR). We studied the response to RA by molecularly analyzing the RA receptor alpha (RAR alpha) locus, which has recently been shown to be rearranged in all APLs. Southern blot analysis demonstrated that the RAR alpha rearrangements persisted in the APL samples containing maturing myeloid cells 2 to 3 weeks after the start of RA treatment, but disappeared after 5 to 8 weeks, when the patients achieved CR. Our investigations provide clear evidence that CR occurs at molecular level and that there is reconstitution of an apparently normal, nonclonal hematopoiesis. Further, it shows that RA acts by triggering differentiation rather than by exerting a cytotoxic effect on the leukemic clone.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/15 - Malattie del Sangue
English
Adult; Aged; Blotting, Southern; Carrier Proteins; DNA, Neoplasm; Female; Gene Rearrangement; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Receptors, Retinoic Acid; Restriction Mapping; Tretinoin; Antineoplastic Agents
Lo Coco, F., Avvisati, G., Diverio, D., Petti, M.c., Alcalay, M., Pandolfi, P.p., et al. (1991). Molecular evaluation of response to all-trans-retinoic acid therapy in patients with acute promyelocytic leukemia. BLOOD, 77(8), 1657-1659.
LO COCO, F; Avvisati, G; Diverio, D; Petti, M; Alcalay, M; Pandolfi, P; Zangrilli, D; Biondi, A; Rambaldi, A; Moleti, M
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/161111
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