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Type and frequency of chromosomal aberrations and importance of molecular JAK2V617F marker in primary myelofibrosis

dc.contributor.advisorPavković-Lučić, Sofija
dc.contributor.otherBogdanović, Andrija
dc.contributor.otherPavlović, Sonja
dc.contributor.otherNovaković, Ivana
dc.creatorĐorđević, Vesna A.
dc.date.accessioned2016-01-05T11:47:49Z
dc.date.available2016-01-05T11:47:49Z
dc.date.available2020-07-03T08:14:20Z
dc.date.issued2013-11-19
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=879
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/2126
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:7282/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=44859663
dc.description.abstractPrimarna mijelofibroza (PMF) je hronična, maligna hematološka bolest, koja se karakteriše leukoeritroblastnom krvnom slikom, anizopoikilocitozom eritrocita u obliku suze, različitim stepenom fibroze kostne srži i hepatosplenomegalijom usled ekstramedularne hematopoeze. Od genetičkih specifičnosti bolesti, ističu se hromozomske aberacije u patološkim, mijeloidnim ćelijama krvi i tačkasta mutacija V617F na genu JAK2. Osnovni cilj studije bio je ispitati kariotipske i citogenetičke parametre i prisustvo mutacije JAK2V617F u genomu bolesnika sa de novo PMF. Ispitani su i drugi dijagnostički parametari, njihove međusobne korelacije i njihov uticaj na kumulativno preživljavanje bolesnika. Analiza kariotipa vršena je konvencionalnom citogenetičkom metodom. Alel-specifična PCR analiza je korišćena za detekciju mutacije JAK2V617F. U studiji su korišćene deskriptivne i analitičke statističke metode. Retrospektivnom analizom citogenetičkih rezultata 61 bolesnika, registrovan je patološki kariotip kod 41% bolesnika. Zastupljene su bile aberacije specifične za PMF: 13q-, 20q-, +8, ali i aberacije ređe zastupljene u ovoj bolesti. Prospektivnom studijom bilo je obuhvaćeno 144 bolesnika. Ispitana je učestalost hromozomskih aberacija u kariotipu bolesnika, učestalost mutacije JAK2V617F, njihova međusobna korelacija i korelacija sa kliničkim i hematološkim, laboratorijskim parametrima. Hromozomske aberacije bile su zastupljene kod 29% bolesnika. Od specifičnih aberacija za PMF, najzastupljenija je bila trizomija hromozoma 9, a zatim 13q- i 20q-. Mutacija JAK2V617F je registrovana kod 55% bolesnika. Ispitivanjem korelacije mutacije i tipa kariotipa, odnosno mutacije i hromozomskih aberacija različitog stepena rizika, nije registrovana statistički značajna razlika (p=0.153). Ispitivanjem značaja kliničkih i hematološko laboratorijskih parametara registrovana je razlika u preživljavanju bolesnika različitih prognoznih grupa primenom Lilskog, Servantesovog, IPSS, DIPSS prognoznih sistema (PS-a) (za sve p<0.001), Mayo PS za sve bolesnike (p=0.001) i Mayo PS za mlađe bolesnike (p=0.013). Ispitivanjem uticaja mutacije JAK2V617F, pokazano je da ne postoji statistički zna čajna razlika (p=0,807) u preživljavanju bolesnika sa i bez mutacije...sr
dc.description.abstractPrimary Myelofibrosis (PMF) is a chronic, malignant hematological disease, characterized by leukoerythroblastic blood picture, anisopoikilocytosis teardrop-shaped erythrocyte, different degree of bone marrow fibrosis and hepatosplenomegaly due to extramedullary hematopoiesis. Among genetic specificities of the disease, those that stand out are chromosomal aberrations in pathological, myeloid blood cells and point mutation V617F in the JAK2 gene. The main goal of study was to examine karyotype and cytogenetic parameters and presence of JAK2V617F mutation in the genome of patients with de novo PMF. Additionally, other diagnostic parameters, their mutual correlations and their effect on cumulative survival rate of patients were examined. Karyotype analysis was performed by conventional cytogenetic method. Allelespecific PCR was used to detect the JAK2V617F mutation. The study used descriptive and analytical statistical methods. By retrospective analysis of cytogenetic results that included 61 patients, abnormal karyotype was registered in 41% of them. Specific PMF aberrations that were found are : 13q-, 20q-, +8, but also aberrations that are rarely present in this disease. Prospective study included 144 patients. The frequency of chromosomal aberrations was tested, so as the frequency of JAK2V617F mutation, their mutual correlation and correlation with clinical and hemato-laboratory parameters. Chromosomal aberrations were present in 29% of patients. Of specific aberrations for PMF, the most common was trisomy of chromosome 9, then 13q-and 20q-. JAK2V617F mutation was registered in 55% of patients. Examining the correlation between mutation and type of karyotype and mutation and chromosomal aberrations with various risk level, statistically significant difference was not registered (p=0.153). Examining the importance of clinical and hematological parameters, difference was registered in survival of patients with different prognostic groups applying Lille, Cervantes, IPSS, DIPSS prognostic systems (PSs) (for all p<0.001), Mayo PS for all patients (p=0.001) and Mayo PS for younger patients (p=0.013)...en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Биолошки факултетsr
dc.rightsopenAccessen
dc.sourceУниверзитет у Београдуsr
dc.subjectHromozomske aberacijesr
dc.subjectChromosomal aberrationsen
dc.subjectmutacija JAK2V617Fsr
dc.subjectprognozni sistemisr
dc.subjectJAK2V617F mutationen
dc.subjectprognostic systemsen
dc.titleTip i učestalost hromozomskih aberacija i značaj molekularnog markera JAK2V617F u primarnoj mijelofibrozisr
dc.titleType and frequency of chromosomal aberrations and importance of molecular JAK2V617F marker in primary myelofibrosisen
dc.typedoctoralThesis
dc.rights.licenseBY-NC-ND
dcterms.abstractПавковић-Лучић, Софија; Новаковић, Ивана; Павловић, Соња; Богдановић, Aндрија; Ђорђевић, Весна A.; Тип и учесталост хромозомских аберација и значај молекуларног маркера ЈAК2В617Ф у примарној мијелофибрози; Тип и учесталост хромозомских аберација и значај молекуларног маркера ЈAК2В617Ф у примарној мијелофибрози;
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/3303/Disertacija.pdf


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