Analiza gena i proteina signalnih puteva Wnt i Sonic Hedgehog u primarnoj i sekundarnoj mijelofibrozi

doctoral thesis

• Title (english): Analysis of genes and proteins of WNT and Sonic Hedgehog signaling pathways in primary and secondary myelofibrosis
• Author: Marko Lucijanić
• Mentor: Rajko Kušec (mentor)
• Committee member: nije dostupno (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2017-04-25, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences
• Universal decimal classification (UDC): 61 - Medical sciences

Abstract

Primarna (PMF) i sekundarna mijelofibroza (SMF) su maligne bolesti hematopoetske matične stanice. WNT i SHH signalni putevi sudjeluju u procesima kontrole stanične diobe, fibroze i neoangiogeneze koji su tipično poremećeni u ovim bolesti.
Imunohistokemijski i lančanom-reakcijom-polimeraze-u-realnom-vremenu (RT-PCR) istražili smo ekspresiju WNT3a, β-katenina, Sklerostina/SOSTa, SHH i GLI1 u ukupno 66 bolesnih (51 PMF, 15 SMF) i 18 zdravih uzoraka koštane srži i korelirali je s kliničkim parametrima.
Elementi kanonskog WNT signalnog puta bili su ukupno jače eksprimirani u PMF i SMF u odnosu na kontrole i mogli bi potencirati anemiju. Ekspresijski profil β-katenina u SMF sličniji je PMF nego izvornim bolestima (PRV/ET). Ekspresija Sklerostina nije se razlikovala u odnosu na kontrole, ali je utjecala na bolje preživljenje bolesnika. Elementi SHH signalnog puta bili su pojačano eksprimirani u megakariocitima oboljelih, ali nisu bili ukupno jače eksprimirani u odnosu na kontrole. SHH ekspresija bila je pojačana u leukemijskoj transformaciji bolesti. Ekspresija pojedinih elemenata kanonskog WNT i SHH signalnih puteva pozitivno korelira zajedno što je u skladu s modelom u kojem ovi putevi čine veću međusobno povezanu mrežu signalnih puteva.
Naši rezultati ukazuju da kanonski WNT i SHH signalni putevi imaju ulogu u patogenezi PMF i SMF.

Abstract (english)

Primary (PMF) and secondary myelofibrosis (SMF) are malignant diseases originating from transformed hematopoietic stem cell. WNT and SHH signaling pathways are involved in processes of cell cycle regulation, fibrosis and neoangiogenesis that are typically deranged in these diseases.
Using immunohistochemistry and real-time-polymerase-chain-reaction (RT-PCR) we investigated WNT3a, β-catenin, Sclerostin/SOST, SHH and GLI1 expression in totally 66 diseased (51 PMF, 15 SMF) and 18 healthy bone marrow samples. Correlations with clinical parameters were made.
Canonical-WNT signaling pathway elements were globally higher expressed in PMF and SMF than in controls and might potentiate anemia. SMF β-catenin expression profile is more similar to PMF than to PRV/ET. Sclerostin expression did not differ between diseased and healthy patients, but positively affected overall survival in diseased patients. SHH signaling pathway elements were higher expressed in megakaryocytes of PMF and SMF than in controls, but were not globally higher expressed. SHH expression was higher in leukemic transformation of disease. Expression of particular elements of both signaling pathways positively correlated together which is in line with the model that these pathways are a part of larger interconnected network.
Our results suggest that canonical-WNT and SHH signaling pathways play a role in pathogenesis of PMF and SMF.

• Keywords: medicina
• Keywords (english): medicine
• Language: croatian
• URN:NBN: urn:nbn:hr:105:736777
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstva (doktor/doktorica znanosti, područje biomedicine i zdravstva)
• Type of resource: Text
• Extent: 97 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-05-05 08:05:01