Literature DB >> 1849758

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

F Lo Coco1, G Avvisati, D Diverio, M C Petti, M Alcalay, P P Pandolfi, D Zangrilli, A Biondi, A Rambaldi, M L Moleti.   

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.

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Year:  1991        PMID: 1849758

Source DB:  PubMed          Journal:  Blood        ISSN: 0006-4971            Impact factor:   22.113


  11 in total

1.  Effects on differentiation by the promyelocytic leukemia PML/RARalpha protein depend on the fusion of the PML protein dimerization and RARalpha DNA binding domains.

Authors:  F Grignani; U Testa; D Rogaia; P F Ferrucci; P Samoggia; A Pinto; D Aldinucci; V Gelmetti; M Fagioli; M Alcalay; J Seeler; F Grignani; I Nicoletti; C Peschle; P G Pelicci
Journal:  EMBO J       Date:  1996-09-16       Impact factor: 11.598

2.  Synergistic inhibition of human rhabdomyosarcoma cells by sodium phenylacetate and Tretinoin.

Authors:  G K Górski; L E McMorrow; M H Donaldson
Journal:  In Vitro Cell Dev Biol       Date:  1993-03

3.  Opposite effects of the acute promyelocytic leukemia PML-retinoic acid receptor alpha (RAR alpha) and PLZF-RAR alpha fusion proteins on retinoic acid signalling.

Authors:  M Ruthardt; U Testa; C Nervi; P F Ferrucci; F Grignani; E Puccetti; F Grignani; C Peschle; P G Pelicci
Journal:  Mol Cell Biol       Date:  1997-08       Impact factor: 4.272

4.  PIC-1/SUMO-1-modified PML-retinoic acid receptor alpha mediates arsenic trioxide-induced apoptosis in acute promyelocytic leukemia.

Authors:  T Sternsdorf; E Puccetti; K Jensen; D Hoelzer; H Will; O G Ottmann; M Ruthardt
Journal:  Mol Cell Biol       Date:  1999-07       Impact factor: 4.272

Review 5.  Management of acute promyelocytic leukemia.

Authors:  Martin S Tallman; Chadi Nabhan
Journal:  Curr Oncol Rep       Date:  2002-09       Impact factor: 5.075

6.  Pulsed-field gel electrophoresis analysis of retinoic acid receptor-alpha and promyelocytic leukemia rearrangements. Detection of the t(15;17) translocation in the diagnosis of acute promyelocytic leukemia.

Authors:  Y H Xiao; W H Miller; R P Warrell; E Dmitrovsky; A D Zelenetz
Journal:  Am J Pathol       Date:  1993-11       Impact factor: 4.307

7.  Retinoic acid mimics transforming growth factor beta in the regulation of human immunodeficiency virus expression in monocytic cells.

Authors:  G Poli; A L Kinter; J S Justement; P Bressler; J H Kehrl; A S Fauci
Journal:  Proc Natl Acad Sci U S A       Date:  1992-04-01       Impact factor: 11.205

8.  Expression pattern of the RAR alpha-PML fusion gene in acute promyelocytic leukemia.

Authors:  M Alcalay; D Zangrilli; M Fagioli; P P Pandolfi; A Mencarelli; F Lo Coco; A Biondi; F Grignani; P G Pelicci
Journal:  Proc Natl Acad Sci U S A       Date:  1992-06-01       Impact factor: 11.205

9.  Genomic variability and alternative splicing generate multiple PML/RAR alpha transcripts that encode aberrant PML proteins and PML/RAR alpha isoforms in acute promyelocytic leukaemia.

Authors:  P P Pandolfi; M Alcalay; M Fagioli; D Zangrilli; A Mencarelli; D Diverio; A Biondi; F Lo Coco; A Rambaldi; F Grignani
Journal:  EMBO J       Date:  1992-04       Impact factor: 11.598

10.  RAR-specific agonist/antagonists which dissociate transactivation and AP1 transrepression inhibit anchorage-independent cell proliferation.

Authors:  J Y Chen; S Penco; J Ostrowski; P Balaguer; M Pons; J E Starrett; P Reczek; P Chambon; H Gronemeyer
Journal:  EMBO J       Date:  1995-03-15       Impact factor: 11.598

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