Using both established human CRLF2/JAK2 mutant B-ALL cells and primary mouse Eμ-Crlf2/Jak2R683G or Eμ-Crlf2/Jak2P933R leukemias, we showed that depletion or inhibition of Jak2 did not affect the viability of these cells but resulted in fewer leukemic cells entering into the cell cycle, which was reflected by a modest therapeutic response in vivo. The gene discussed is CRLF2; the disease is leukemia.