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Inhibition of acute lymphoblastic leukaemia by a Jak-2 inhibitor


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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Meydan, N., Grunberger, T., Dadi, H. et al. Inhibition of acute lymphoblastic leukaemia by a Jak-2 inhibitor. Nature 379, 645–648 (1996).

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