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Inhibition of acute lymphoblastic leukaemia by a Jak-2 inhibitor

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Abstract

ACUTE lymphoblastic leukaemia (ALL) is the most common cancer of childhood. Despite the progress achieved in its treatment, 20% of cases relapse and no longer respond to chemotherapy. The most common phenotype of ALL cells share surface antigens with very early precursors of B cells and are therefore believed to originate from this lineage1,3Characterization of the growth requirement of ALL cells indicated that they were dependent on various cytokines, suggesting paracrine and/or autocrine growth regulation4–6. Because many cytokines induce tyrosine phosphorylation in lymphoid progenitor cells, and constitutive tyrosine phosphorylation is commonly observed in B-lineage leukaemias7,8, attempts have been made to develop protein tyrosine kinase (PTK) blockers of leukaemia cell growth9,10. Here we show that leukaemic cells from patients in relapse have con-stitutively activated Jak-2 PTK. Inhibition of Jak-2 activity by a specific tyrosine kinase blocker, AG-490, selectively blocks leukaemic cell growthin vitro and in vivo by inducing programmed cell death, with no deleterious effect on normal haematopoiesis.

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Author notes

  1. Chaim M. Roifman: To whom correspondence should be addressed.

Authors and Affiliations

  1. Divisions of Immunology/Allergy, Haematology and Pharmacology, The Hospital for Sick Children, and the Department of Pediatrics, University of Toronto, Toronto, M5G 1X8, Canada

    Naftaly Meydan, Tom Grunberger, Harjit Dadi, Michal Shahar, Enrico Arpaia, J. Steven Leeder, Melvin Freedman, Amos Cohen & Chaim M. Roifman

  2. Department of Immunology, The Weizmann Institute, Rehovot, Israel

    Zvi Lapidot

  3. Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University, Jerusalem, Israel

    Aviv Gazit & Alexander Levitzki

Authors
  1. Naftaly Meydan
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  2. Tom Grunberger
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  3. Harjit Dadi
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  4. Michal Shahar
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  5. Enrico Arpaia
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  6. Zvi Lapidot
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  7. J. Steven Leeder
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  8. Melvin Freedman
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  9. Amos Cohen
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  10. Aviv Gazit
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  11. Alexander Levitzki
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  12. Chaim M. Roifman
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Meydan, N., Grunberger, T., Dadi, H. et al. Inhibition of acute lymphoblastic leukaemia by a Jak-2 inhibitor. Nature 379, 645–648 (1996). https://doi.org/10.1038/379645a0

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  • DOI: https://doi.org/10.1038/379645a0

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