JAK2 Mutations in Chronic Myeloproliferative Neoplasm;Towards the Application of Personalized Treatments for Saudi Patients

作     者：Mamdooh Gari Fatin Al-Sayes Farid Ahmed Abdul Ali Peerzada Adel Abuzenadah Lubna S. Mira Mohammed Al-Qahtani Ashraf Dallol Adeel Chaudhary Mohammed Mahnashi Ghazi Damanhouri 

作者机构：Center of Excellence in Genomic Medicine Research King Abdulaziz University Jeddah Saudi Arabia Clinical Hematology Laboratory King Abdulaziz Hospital and Oncology Center Jeddah Saudi Arabia Department of Hematology Faculty of Medicine King Abdulaziz University Jeddah Saudi Arabia Department of Medical Laboratory Technology Faculty of Applied Medical Sciences King Abdulaziz University Jeddah Saudi Arabia 

出 版 物：《Open Journal of Blood Diseases》 (血液病期刊（英文）)

年 卷 期：2012年第2卷第2期

页      面：17-21页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Leukemia CMPN PV ET PMF JAK2 Mutation 

摘      要：The chronic myeloproliferative neoplasms (CMPN) are a group of clonal hematopoietic stem cell disorders in which large numbers of red blood cells, white blood cells, or platelets grow and spread excess in the bone marrow and the pe- ripheral blood. Cytogenetic analysis of the t (9:22) and molecular detection of BCR/ABL is the main diagnostic criteria in Philadelphia positive CMPN (CML). The identification of non-receptor tyrosine kinase JAK2 mutations (exon 14 JAK2 V617F and exon 12) have significantly contributed to our understanding of the molecular mechanisms in the pathogenesis of Philadelphia negative CMPN such as polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients. According to the revised WHO classification, JAK2 mutation is considered as a major diagnostic and clonal marker in Philadelphia negative CMPN which will play a major role in designing personal- ized treatments for the disease. JAK2 V617F mutation frequency is unknown in Saudi Arabia. Therefore, investigation of the JAK2 V617F mutation was carried out in DNA samples from 78 peripheral blood specimens corresponding to patients with polycythemia vera (PV) (n = 11), Chronic myeloid leukemia (CML) (n = 45), essential thrombocythemia (ET) (n = 10), idiopathic myelofibrosis (MF) (n = 12). We used polymerase chain reaction and direct DNA sequencing to detect the JAK2 mutation. Overall, the incidence of the JAK2 V617F mutation was 91% in PV, 40% in ET, and 25% in MF. This approach proved to be reliable and more sensitive in detecting the mutation. Two essential findings arose from our study. First, this technique could be carried out with DNA samples, even partially degraded, from routinely processed BM or peripheral blood specimens. Second, after correlation with morphological features, it turned out that the characteristics of the megakaryocytes were more specific than the mutational status of JAK2 in characterizing ET and PMF. Concerning PV, as expected, the in