الفهرس 
Title pageOnly 14 pages are availabe for public view
 |  | from | 16 |  |  |
| | | from | 16 | | |
Abstract
Myeloproliferative neoplasms (MPNs) are malignancies where there is an uncontrolled increase in the formation of the myeloid cells. The classic Philadelphia chromosome negative MPNs include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). A mutation (V617F) in the tyrosine kinase, Janus kinase 2, has been found to be the cause of at least three of the classical MPNs. The mutation lies in the domain of the protein that controls its tyrosine kinase activity. JAK2 V617F represents a G to T somatic mutation at nucleotide 1849, in exon 14 is a gain of function mutation that contributes to the expansion of the MPN clone by increasing the tyrosine phosphorylation activity that promotes cytokine activity.
The clinical presentation and laboratory findings of these diseases is variable, but common elements can include splenomegaly, increased risk of thrombosis and/or bleeding, overproduction of one or more of the myeloid cell lines, bone marrow hyper cellularity with or without fibrosis.
Several studies have shown that the prevalence of the JAK2-V617F mutation in PV is very high, ranging from 65 to 100 %; in contrast, only approximately 23–69 % of patients with ET and PMF are JAK2-V617F positive.
The aim of the work is to detect the JAK2 V617F mutation in Polycythemia vera, essential thrombocythemia and primary myelofibrosis. This will allow proper diagnosis and management of affected cases.
This study was conducted on 57 patients of newly and previously diagnosed cases of Ph negative myeloproliferative diseases using the WHO 2008 Criteria (20 patients were PV, 21 were ET and 16 were PMF). These patients were recruited from Mansoura university hospital oncology and hematology clinics, beginning from December 2013 till November 2014. In addition to fifty five healthy individuals were randomly selected from the volunteers with matched age and sex.
The results of the current study revealed the following:
1- In our study no one of the control group (0%) had shown JAK2 mutation expression while in MPNs patients, 37 patients (64.9 %) had JAK2 mutation expression and 20 patients (35.1%) had wild type.
2- Twenty nine out of 57 patients (50.9%) were heterozygous JAK2V617F mutation, while 8 out of 57 (14%) were homozygous mutation.
3- The frequency of JAK2V617F mutation in PV,ET and PMF was as the following:
A. In PV patients: the JAK2V617F mutation was identified in 16 out of 20 patients (80%). Five patients (25%) expressed homozygous mutation, while eleven (55%) expressed heterozygous mutation.
B. In ET patients: Out of the studied twenty one patients, eleven (52.4%) had JAK2V617F mutation. One of 21 ET patients (4.8%) was homozygous mutation while ten out of 21(47.6%) were heterozygous.
C. In PMF patients: the molecular testing detected a V617F mutation in ten out of sixteen patients (62.5%), two patients (12.5%) were homozygous while eight (50%) showed heterozygous mutation.
4- On comparing mutant JAK2 V617F allele and wild type allele in PV, ET and PMF patients according to Hb and platelets, there was no statistical significant difference between the two groups, and also in PV and ET patients regarding WBCs. But there is statistical significant difference between mutant and normal PMF patients where the mutant have higher mean of WBCs count.
5- Splenomegaly was more prevalent in the patients with positive mutation than in patients with negative mutation in PV and ET in contrast to PMF patients where the splenomegaly was more frequent in the negative cases.
JAK2V617F mutation detected by ARMS-PCR provides a specific method that can be useful in confirming the diagnosis of MPNs.
The identification of activating mutations in the JAK2 signaling pathway in PV, ET and PMF provides an opportunity to develop molecularly targeted therapies for patients with these disorders.