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Orchestration of multiple arrays of signal cross-talk and combinatorial interactions for maturation and cell death: another vision of t(15;17) preleukemic blast and APL-cell maturation

Oncogene volume 20, pages 7161–7177 (2001)Cite this article

Abstract

Despite intensive molecular biology investigations over the past 10 years, and an important breakthrough on how PML–RARα, the fusion protein resulting from t(15;17), can alter RARα and PML functions, no definitive views on how leukemia is generated and by what mechanism(s) the normal phenotype is restored, are yet available. ‘Resistances’ to pharmacological levels of all-trans-retinoic acid (ATRA) have been observed in experimental in vivo and in vitro models. In this review, we emphasize the key role played by signal cross-talk for both normal and neoplastic hemopoiesis. After an overview of reported experimental data on APL-cell maturation and apoptosis, we apply our current knowledge on signaling pathways to underline those which might generate signal cross-talks. The design of biological models suitable to decipher the integration of signal cross-talks at the transcriptional level should be our first priority today, to generate some realistic therapeutic approaches After ‘Ten Years of Molecular APL’, we still know very little about how the disease develops and how effective medicines work.

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Acknowledgements

M Lanotte would like to thank Dr Jean-Michel Miclea (Blood Transfusion Department, St-Louis Hospital, Paris, France) for helpful discussions and passing on Claude Bernard's statement that corresponds so well to the research situation after ten years of molecular APL: ‘In medicine, we do much more than we understand.’ GR Benoit benefited from a fellowship from the Association pour la Recherche contre le Cancer (ARC). This work was supported by funds from the Institut National de la Santé et de la Recherche Médicale (INSERM) and research grants from the Ligue Nationale contre le Cancer and ARC.

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  1. INSERM U-496, Hópital Saint-Louis, 1, avenue Claude-Vellefaux, Paris, 75010, France

    Gérard Benoit, Mathilde Roussel, Frédério Pendino, Evelyne Ségal-Bendirdjian & Michel Lanotte

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  1. Gérard Benoit
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  2. Mathilde Roussel
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  3. Frédério Pendino
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  5. Michel Lanotte
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Correspondence to Michel Lanotte.

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Benoit, G., Roussel, M., Pendino, F. et al. Orchestration of multiple arrays of signal cross-talk and combinatorial interactions for maturation and cell death: another vision of t(15;17) preleukemic blast and APL-cell maturation. Oncogene 20, 7161–7177 (2001). https://doi.org/10.1038/sj.onc.1204760

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