THE ROLE OF JAK2 INHIBITORS IN THE MANAGEMENT OF CML: CAN WE REST THE CASE?

2014 Science Proceedings  
Chronic myeloid leukaemia (CML) is a clonal myeloproliferative disorder arising as a result of the reciprocal translocation between the long arms of chromosomes 9 and 22 (t9;22), leading to the formation of the fusion oncogene BCR-ABL. BCR-ABL has constitutive tyrosine kinase (TK) activity which is necessary for the transformed phenotype. The introduction at the end of the last century of BCR-ABL TK inhibitors (TKI) has dramatically changed the management of CML however despite their great
more » ... acy, TKI are not curative. Disease persistence in CML patients treated with TKI lies in the insensitivity of the most primitive CML leukaemia stem cell (LSC). CML LSCs are not addicted to BCR-ABL kinase activity but rather rely on other stem cell intrinsic pathways for their survival. The main focus in the CML field is therefore to identify these pathways while also trying to exploit them therapeutically to achieve CML LSC eradication and as a result disease cure. Here we briefly review recent research on the role of the intracellular janus kinase (JAK) 2 in CML LSC survival and proliferation and discuss its putative role as a therapeutic target in CML. We discuss evidence supporting or dismissing a role for JAK2 in CML LSC survival and provide a possible explanation to reconcile the contrasting data published. We finally outline the future challenges which lie ahead of the CML community in trying to elucidate further the mechanisms of action of JAK2 and to translate into clinical practice the use of JAK2 inhibitors in CML. To cite this article: Paolo Gallipoli. The role of jak2 inhibitors in the management of cml: can we rest the case. Sci Proc 2014; 1: e383.
doi:10.14800/sp.383 fatcat:rvpa5b4gubekdkmbv5k6v6zmfm