Constitutively activated mutants of the non-receptor tyrosine kinases (TK) ABL1 
(Abelson murine leukemia viral (v-abl) homolog (1) protein) and JAK2 (JAnus 
Kinase 2 or Just Another Kinase 2) play a central role in the pathogenesis of 
clinically and morphologically distinct chronic myeloproliferative disorders but 
are also found in some cases of de novo acute leukemia and lymphoma. 
Ligand-independent activation occurs as a consequence of point mutations or 
insertions/deletions within functionally relevant regulatory domains (JAK2) or 
the creation of TK fusion proteins by balanced reciprocal translocations, 
insertions or episomal amplification (ABL1 and JAK2). Specific abnormalities are 
correlated with clinical phenotype, although some are broad and encompass 
several World Health Organization-defined entities. TKs are excellent drug 
targets as exemplified by the activity of imatinib in BCR-ABL1-positive disease, 
particularly chronic myeloid leukemia. Resistance to imatinib is seen in a 
minority of cases and is often associated with the appearance of secondary point 
mutations within the TK domain of BCR-ABL1. These mutations are highly variable 
in their sensitivity to increased doses of imatinib or alternative TK inhibitors 
such as nilotinib or dasatinib. Selective and non-selective inhibitors of JAK2 
are currently being developed, and encouraging data from pre-clinical 
experiments and initial phase-I studies regarding efficacy and potential 
toxicity of these compounds have already been reported.