INHIBITION OF ACUTE LYMPHOBLASTIC-LEUKEMIA BY A JAK-2 INHIBITOR

ACUTE lymphoblastic leukaemia (ALL) is the most common cancer of child hood. Despite the progress achieved in its treatment, 20% of cases rel apse and no longer respond to chemotherapy. The most common phenotype of ALL cells share surface antigens with very early precursors of B ce lls and are therefore believed to originate from this lineage(1,3). Ch aracterization of the growth requirement of ALL cells indicated that t hey were dependent on various cytokines, suggesting paracrine and/or a utocrine growth regulation(4-6). Because many cytokines induce tyrosin e phosphorylation in lymphoid progenitor cells, and constitutive tyros ine phosphorylation is commonly observed in B-lineage leukaemias(7,8), attempts have been made to develop protein tyrosine kinase (PTK) bloc kers of leukaemia cell growth(9,10). Here we show that leukaemic cells from patients in relapse have constitutively activated Jak-2 PTK. Inh ibition of Jak-2 activity by a specific tyrosine kinase blocker, AG-49 0, selectively blocks leukaemic cell growth in vitro and in vivo by in ducing programmed cell death, with no deleterious effect on normal hae matopoiesis.