Journal of Biological Chemistry by jbc at NYU School of Medicine Library, 6 M Downloaded March, 2012 Page 7 T-cell precursor Shore of acute leukemia Chemistry lymphocytic KSP Inhibitors leukemia leukemia (ALL). 9 patients with ALL JAK1 mutation had significantly reduced disease-free survival and overall survival compared to patients without the mutation. The discovery of a mutation of tyrosine kinase activation known JAK2V617F in myeloproliferative disorders (MPN) Has produced polycythemia vera (PV), essential Thrombozyth Chemistry (ET) and myelofibrosis (PMF) as  big interest in it as a potential approach targeting JAK2 for the treatment of MPN. 10 The mutation in the pseudokinase Dom ne of JAK2 enzyme and leads to reduced F Ability of the pseudo kinase Dom ne mutated to negatively regulate the kinase Dom ne (an active part of an enzyme) of JAK2. 11 Unaudited JAK2 activation, a key enzyme in growth factor signaling and numerous cytokines is believed to be r Important role in the pathophysiology of the MPN.

Almost all patients with PV and longer than the H Half of patients with ET and PMF are JAK2V617F mutation, albeit at different levels from the burden of the allele (this ratio Ratio of mutated DNA and JAK2V617F total JAK2 DNA). 12 Al when JAK2V617F seems the h Most frequent mutation with MPN, other mutations which activate abnormal JAK2 were Marbofloxacin also determined (eg, the MPL receptor MPLW515LKin, 13 and other JAK2 mutation in exon 12 may be resident assigned ) 14 in the small percentage of patients with PN who had not JAK2V617F mutation. All these mutations confer hypersensitivity against, or Independent Dependence of h Hematopoietic cytokines Ethical, which then causes no abnormal proliferation and survival of stem cells influenced.

The forced expression of these mutations in mice M, Either by transgenic expression or retroviral transfer of bone marrow stem cells, suggesting the results of PV, ET and post-PVET myelofibrosis (MF) Ph Genotype, an r potentially urs chliche mutations in the MPN. Recently, three groups have independently Of one another Ver published shall study a genetic haplotype that identify sp To detailed development of the JAK2V617F mutation and MPN pr And thus predisposed to the evidence of a hereditary predisposition to develop JAK2V617F mutation through somatic mutation. 15-17 These reports are also on the growing evidence that the mutation JAK2V617F is not an anomaly caused MPN heart contributed, but satisfied T is a factor for the existence of the disease. 18.19 Identification of anomalies that lead to the existence of MPN, and separate entities clinics PV, ET and PMF in humans is a subject of intense research. 20.21 JAK2 as a therapeutic target for the discovery of imatinib, BCR-ABL kinase inhibitor, big s progress in the development of kinase inhibitors with exquisite selectivity Has been made t and effectiveness. Most drug discovery efforts on the identification of kinase inhibitors have focused on ATP-mimetic inhibitors H Hematology small molecules 2 9th 22, because a tyrosine kinase JAK2, is the discovery of activating mutations leads naturally to a big s excitement and optimism in the identification and development of JAK2 inhibitors for the treatment of the MPN. 23 JAK2V617F  utated enzyme is often compared with the BCR-ABL oncoprotein in relation to the development of drugs. 24 However, since no known function unerl Ugly to the endogenous ABL kinase-ID was.