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Signal Transduction

A transient dephosphorylation of JAK1 and JAK2 characterises the early-phase response of murine erythroleukemia cells to the differentiation inducer hexamethylenebisacetamide

Leukemia volume 14, pages 2112–2117 (2000)Cite this article

Abstract

Although dephosphorylation of tyrosine containing proteins is considered a necessary step in the induction of leukemia cell differentiation by hybrid polar compounds (HPC), the crucial actors in this step remain unknown. We present evidence that tyrosine phosphorylation of JAK1 and JAK2 is down-regulated in murine erythroleukemia cells (MELC) within the first 6 h of their exposure to the prototype of the HPC family, hexamethylenebisacetamide (HMBA), with full recovery at 14 h. Further evidence that the JAKs-centered signalling pathway is switched off early by HMBA was provided by the demonstration that STAT5, a downstream member of this pathway, turned out to be completely dephosphorylated at 6 h in HMBA-treated cells. This JAKs dephosphorylation did not occur in HMBA-resistant clones, suggesting that JAKs are possible targets of the dephosphorylative process required for leukemia cell commitment to differentiation. These results may have impact on leukemia therapy based on JAKs inhibitors.

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Acknowledgements

This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC), Associazione Italiana contro le Leucemie (AIL) Firenze, Ministero dell'Università e della Ricerca Scientifica e Tecnologica (MURST). The authors are indebted to Dr RA Rifkind, chairman of the Sloan-Kettering Institute of New York, for support and advice. The authors are grateful to Prof A Fonnesu and Dr Persio Dello Sbarba for helpful suggestions, and to Marco Cutrì for skilful technical assistance. The authors are also grateful to Dr P Bernabei for help and advice in the morphological examination of MELC.

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Authors and Affiliations

  1. Department of Experimental Pathology and Oncology, University of Firenze, Firenze, Italy

    A Arcangeli, L Fontana, O Crociani, A Cherubini, G Hofmann, E Piccini, S Polvani, M D'Amico & M Olivotto

  2. Department of Physics, University of Firenze, Firenze, Italy

    M Carlà

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  1. A Arcangeli
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  2. L Fontana
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Arcangeli, A., Fontana, L., Crociani, O. et al. A transient dephosphorylation of JAK1 and JAK2 characterises the early-phase response of murine erythroleukemia cells to the differentiation inducer hexamethylenebisacetamide. Leukemia 14, 2112–2117 (2000). https://doi.org/10.1038/sj.leu.2401936

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