Tip i učestalost hromozomskih aberacija i značaj molekularnog markera JAK2V617F u primarnoj mijelofibrozi
Type and frequency of chromosomal aberrations and importance of molecular JAK2V617F marker in primary myelofibrosis
Докторанд
Đorđević, Vesna A.Ментор
Pavković-Lučić, SofijaЧланови комисије
Bogdanović, AndrijaPavlović, Sonja
Novaković, Ivana
Метаподаци
Приказ свих података о дисертацијиСажетак
Primarna 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...
Primary 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 include...d 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)...