Kliničko značenje bjelančevine 1 slične hitinazi-3 i hitotriozidaze u bolesnika s Philadelphia negativnim mijeloproliferativnim neoplazmama

doctoral thesis

• Title (english): Clinical significance of chitinase-3-like protein 1 and chitotriosidase in Philadephia-negative myeloproliferative neoplasms
• Author: Ivan Krečak https://orcid.org/0000-0002-8642-305X
• Mentor: Nadira Duraković (mentor)
• Committee member: Radovan Vrhovac (predsjednik povjerenstva)
• Committee member: Rajko Kušec (član povjerenstva)
• Committee member: Slavko Gašparov (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2020-06-05, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine
• Universal decimal classification (UDC): 616 - Pathology. Clinical medicine

Abstract

Philadelphia negativne mijeloproliferativne neoplazme (MPN), esencijalna trombocitemija (ET),
policitemija vera (PV) i mijelofibroza (MF), su bolesti karakte rizirane klonalnom
mijeloproliferacijom, snažnom upalnom atmosferom i p ovećanim rizikom od kardiovaskularnih
(KV) događaja. YKL 40 i hitotriozidaza (CHIT1) imaju važnu ulog u u reguliranju upalnog
odgovora i vanstaničnom remodeliranju tkiva Cilj ovog istraživanja bio je analizirati izražaj
serumske koncentracije YKL 40 i a kti vnosti CHIT1 u bolesnika s MPN te ga korelirati s kliničkim
značajkama bolesti. Koristeći imunoenzimski test i fluorometrijsku metodu analizira li smo
cirkulirajuće vrijednosti YKL 40 i CHIT1 u 111 bolesnika s MPN i u 32 zdrava dobrovoljca. Svi
entiteti unutar MPN spektra su i ma li povišen YKL 40, dok su samo „policitemični“ bolesnici PV i
post PV MF imali i značajno povišen CHIT1. YKL 40 i CHIT1 su u bolesnika s MPN koreliral i s
parametrima povezanim s većim tumorskim opterećenjem i snažnijim upalnim zbivanjem ( C
reaktivnim proteinom , prisutnošću konstitucijskih simptoma, lošijim općim tjelesnim stanjem i KV
rizičnim čimbenicima )). U multivarijatnim analizama preživljenja , povišen YKL 40 je u bolesnika s
ET i PV bi o rizični čimbenik za razvoj tromboze, a u bolesnika s MF i prediktor lošijeg preživljenja.
Naši rezultati impliciraju patofiziološku ulogu hitinaza i hitinazama sličnih proteina u patogenezi
MPN, a mogli bi pomoći i u identificiranju novih terapijskih pristupa

Abstract (english)

Philadelphia negative myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET),
polycythe mia vera (PV) and myelofibrosis (MF), are characterized by clonal myeloproliferati on
strong inflammatory atmosphere , and an increased cardiovascular (CV) burden . YKL 40 and serum
chitotriosidase activity (CHIT1) have an important role in atherosclerotic i nflammation and tissue
remodelling. The aim of this study was to investigate circulating YKL 40 and CHIT1 in patients
with MPNs and to assess its clinical correlations. Enzyme linked immunosorbent assay and
flurometry we're used to analyze serum YKL 40 conc ent rations and CHIT1 activity in 111 MPN
patients and in 32 healthy controls, respectively. YKL 40 w as higher in MPNs when compared to
healthy controls, whereas CHIT1 was higher only in the “polycythemic” disorders ( PV and post PV
M F )). Higher circulating Y KL 40 and CHIT1 were associated with parameters indicative of the
increasedinf lammatory state (C reactive protein, poor performance status, presence of
constitutional symptoms and CV risk factors). Higher YKL 40 was associated with an increased
risk of thrombosis in ET and PV, as well as with impaired survival in MF pa tients These results
implicate a role of chitinases and chitinase like proteins in the pathogenesis of MPNs. Further
studies are needed to elucidate if these circulating MPN biomarkers might be a novel therapeutic
targets in MPNs.

• Keywords: esencijalna trombocitemija; policitemija vera: mijelofibroza; YKL 40; hitotriozidaza
• Keywords (english): essential thrombocythemia; polycythemia vera; myelofibrosis; YKL 40; chitotriosidase
• Language: croatian
• URN:NBN: urn:nbn:hr:105:134991
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Catalog URL: https://katalog.nsk.hr/F/19IT7Y755V1NXQJPHCLYSQGPF6BLAPPF179HQ7FAXXMYBYGMV5-08163?func=find-e&request=Klini%C4%8Dko+zna%C4%8Denje+bjelan%C4%8Devine+1+sli%C4%8Dne+hitinazi-3+i+hitotriozidaze+u+bolesnika+s+Philadelphia+negativnim+mijeloproliferativnim+neoplazmama&find_scan_code=FIND_NAS&adjacent=N&local_base=MF_WEB&x=0&y=0&filter_code_1=WLN&filter_request_1=&filter_code_2=WYR&filter_request_2=&filter_code_3=WYR&filter_request_3=&filter_code_4=WFM&filter_request_4=
• Type of resource: Text
• Extent: 107 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-03-08 10:57:44