Title Analiza Aurora kinaza A / Polo kinaza 1 signalnog puta u oboljelih od mijelofibroze Title (english) Aurora kinase A / Polo-like kinase 1 signaling pathway analysis in patients with myelofibrosis Author Davor Galušić Mentor Rajko Kušec (mentor)Committee member Ivana Marinović Terzić (predsjednik povjerenstva)Committee member Merica Glavina Durdov (član povjerenstva)Committee member Igor Aurer (član povjerenstva)Granter University of Split Defense date and country 2021, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 616 - Pathology. Clinical medicine Abstract Aurora kinaza A (AURKA), protein Aurora borealis (BORA), Polo-like kinaza 1
(PLK1) i Cell-division-cycle 25c (CDC25c) kontroliraju stanični ciklus i ulazak stanice u
mitozu, a njihova disregulacija opisana je u brojnim malignim bolestima. Cilj rada bio je ispitati
do sad nedovoljno istražen izražaj njihovih mRNA u mijeloproliferativnoj bolesti, mijelofibrozi
(MF). Iz citoloških punktata koštane srži urađena je PCR mRNA analiza navedenih gena u 43
bolesnika s mijelofibrozom, i to 28 s primarnom (PMF) i 15 sa sekundarnom mijelofibrozom
(SMF). U kontrolnim skupinama bilo je 12 ispitanika s agresivnim ne-Hodgkinovim limfom
bez infiltracije koštane srži i 6 ispitanika s reaktivnom promjenom koštane srži bez zloćudne
bolesti. Optimalne granične vrijednosti izražaja mRNA za diskriminaciju preživljenja odabrane
su korištenjem analize ROC krivulje. Nije bilo značajne razlike u izražaju AURKA mRNA
između ispitanika s MF i kontrolnih ispitanika (P=0.466). Viša vrijednost izražaja AURKA
mRNA značajno je povezana s većim apsolutnim brojem monocita (P=0.024) i kraćim ukupnim
preživljenjem (HR=3.77; P=0.012). U bolesnika s PMF i SMF značajno je niži izražaj BORA
mRNA u odnosu na kontrolne ispitanike (P=0.009). Viša vrijednost izražaja BORA mRNA
značajno je povezana s povoljnim prognostičkim pokazateljima: odsutnošću konstitucijskih
simptoma (P=0.049) i cirkulirajućih blasta (P=0.047), ali bez značajne povezanosti s ukupnim
preživljenjem (P>0.05). Nije bilo značajne razlike u izražaju PLK1 mRNA između ispitanika s
MF i kontrolnih ispitanika (P=0.103). Viša vrijednost izražaja PLK1 mRNA značajno je
povezana s većim ukupnim brojem leukocita (P=0.042) i kraćim ukupnim preživljenjem
(HR=5.87; P=0.003). Nije bilo značajne razlike u izražaju CDC25c mRNA između ispitanika
s MF i kontrolnih ispitanika (P=0.162). Viša vrijednost izražaja CDC25c mRNA značajno je
povezana s nepovoljnim prognostičkim pokazateljima: većom jetrom (P=0.022), većim
ukupnim brojem leukocita (P=0.017), većim apsolutnim brojem neutrofila (P=0.010), monocita
(P=0.050), bazofila (P=0.012) i eozinofila (P=0.013) te kraćim ukupnim preživljenjem
(HR=2.99; P=0.049). Izražaj ovih gena ima utjecaj na ukupno preživljenje u mijelofibrozi te
istraživanje treba proširiti na druge hematološke zloćudne bolesti i one s reaktivnim i prolaznim
promjenama hematopoeze.
Abstract (english) Aurora kinase A (AURKA), Aurora borealis protein (BORA), Polo-like kinase 1
(PLK1) and Cell-division-cycle 25c (CDC25c) are required for cell cycle control and promotion
of mitosis entry. Their dysregulation has been described in a number of malignant diseases.
However, their role in pathogenesis of myelofibrosis is less known. We investigated AURKA,
BORA, PLK1 and CDC25c mRNA expression in bone marrow aspirates of 43 patients with
myelofibrosis (28 primary - PMF, 15 secondary myelofibrosis - SMF) and 18 controls (the first
control group of 12 with limited stage of aggressive non Hodgkin lymphoma without bone
marrow involvement and the second group of 6 with nonmalignant reactive bone marrow).
Optimal cut-off values for dichotomization of expression levels of investigated genes for the
purpose of survival analysis were done using the ROC curve analysis with survival status as a
classification variable. AURKA mRNA expression did not significantly differ between
myelofibrosis and controls (P=0.466). Higher AURKA expression was significantly associated
with higher absolute monocyte count (P=0.024) and shorter overall survival (HR=3.77;
P=0.012). Patients with both PMF and SMF had lower BORA mRNA expression than controls
(P=0.009). Higher BORA expression was significantly associated with favourable prognostic
factors: absence of constitutional symptoms (P=0.049) and absence of circulatory blasts
(P=0.047), but with neutral effect on survival (P>0.05). PLK1 mRNA expression did not
significantly differ between myelofibrosis and controls (P=0.103). Higher PLK1 expression
was significantly associated with higher white blood cell count (P=0.042) and inferior overall
survival (HR=5.87; P=0.003). CDC25c mRNA expression did not significantly differ between
myelofibrosis and controls (P=0.162). Higher CDC25c mRNA was significantly associated
with unfavourable prognostic factors: higher white blood cells count (P=0.017), larger liver size
(P=0.022), higher absolute neutrophil (P=0.010), monocyte (P=0.050), basophil (P=0.012) and
eosinophil counts (P=0.013) and inferior overall survival (HR=2.99; P=0.049). In conclusion,
these genes effects survival and seem to be involved in pathogenesis of myelofibrosis. Future
studies investigating these genes in hematological malignancies, as well as in reactive disorders,
are warranted.
Keywords
primarna mijelofibroza
Aurora kinaza A
transdukcija signala
Keywords (english)
Primary Myelofibrosis
Aurora Kinase A
Signal Transduction
Language croatian URN:NBN urn:nbn:hr:171:821922 Study programme Title: Evidence-Based Clinical Medicine Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2023-05-03 13:24:41
