Patients with Down syndrome, myeloproliferative leukemia Mie type With acute Megakaryoblastic and in some F Cases severe combined immunodeficiency can TYK2 9 11 and an r lymphoid neoplasms in of natural killer cells and functional defects.12 JAK2 JAK2  in 1992 by Pritchard and colleagues, 13 It has 140 kb covering exons 25 amino acids AC480 BMS-599626 to 1132 JAK2 protein.14 It acts as a signaling molecule for many cytokines form below: INF 15 rythropo retina, 16 prolactin 17 thrombopo retina, G-CSF, GM and IL CSF18 319 through the activation of multiple signal transduction pathways, such as: seem MAPK, PI3, 16 and ERK20 STATs.14 PRV1 and NF E2also activated and overexpressed by JAK2 0. 6 one of the key signaling pathways by JAK2 STAT5 are activated by the activation of the BCL XL and nally enter the up-regulation of the cell where BCL2 gain survive advantage.6 types of anomalies and pathogenesis JAK2 normally followed rearrangements 4.21 CP-466722 25 A.: can in 4 categories be divided TEL/ETV6: JAK2 can be rearranged t as reported in some CML cells MPN and T ALL, BCR: t as reported in some CML MPN PCM1: t reported in some MPN, AML and ALL, NF E2: the t reported in some F cases of MDS. B. Point mutations V617F GT nucleotides 1849 exon14 in MPN Haupt Chlich classic T875N in AML, R683G and less h all Frequently other R683 mutations in 18 28% of patients with Down syndrome and reported reported 10% of a high-risk cohort of childhood patients without Down syndrome. C. deletions / insertions Exon12: There are reported more than eight mutations, deletions and insertions in codons 538-543 of the report ed in 4% of F lle of PV is IREED del five amino acid deletion in the JH2 pseudokinase domain reported in B-cell ALL patients with Down’s syndrome. D. It can be presented as a digital trisomy or overexpressed by amplification. The majority of these abnormalities affect JH2 Dom ne, the loss of the inhibitory effect on ne JH1 Dom, where the sp is Ter automatically. Suppressor of cytokine signaling 1 and 3 are negative regulators of JAK2 kinase, these suppressors are also phosphorylated and stabilized by the hyperactive tyrosine kinase.26 SOCS3 promoter methylation is another mechanism which can be found in a group of patients are reported 0.27 ht have that 5 to 10% of patients NPP at least one parent who is affected by this disease, and the family MPN increased risk for developing this disease fold. 6 6, 28 Recent studies suggest that single nucleotide polymorphisms individuals are equipped with a h Heren risk for developing JAK2 V617F mutation associated. about 659 SNPs rs10974944 and rs12343867 were in 77% and 85% reported in association with the JAK2 V617F mutation, each with a significant difference from the wild type JAK2.29 Pr prevalence of h dermatological malignancies compared JAK2 V617F mutation in JAK2 is only reported in myeloproliferative neoplasms with a high frequency in PV, ET, PMF refractory to re chemistry with ring and sideroblast and thrombocytosis. It is rare in CML, saw 30, but not in all or molecularly characterized eosinophilic tumors and mastocytosis, ie those who have abnormalities in PDGFRA, PDGFRB, FGFR1 or KIT.