Međudjelovanje gena stromalnih stanica i gena krvotvornih matičnih stanica u primarnoj mijelofibrozi

doctoral thesis

• Title (english): Cell-stroma interacting genes in patients with primary myelofibrosis
• Author: Ana Livun
• Mentor: Rajko Kušec (mentor); MBZ: 81895
• Committee member: Maruška Marušić (član povjerenstva)
• Committee member: Rajko Kušec (član povjerenstva); MBZ: 81895
• Committee member: Nada Oršolić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2013, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 575 - General genetics. General cytogenetics

Abstract

Primarna mijelofibroza (PMF) je agresivna i rijetka bolest karakterizirana fibrozom koštane srži (KS), leukoeritroblastozom te hematopoezom van KS u povećanoj slezeni i jetri. U perifernoj krvi (PK) povećan je broj cirkulirajućih krvotvornih matičnih stanica CD34+. U 32 bolesnika izmjeren je izražaj SPARC i CXCR4 odgovornih za komunikaciju stromalnih stanica mikrookoliša i CD34+ stanica u mononuklearima KS i PK te uspostavljenoj kulturi stromalnih i hematopoetskih stanica. Istraživanje je prošireno na gene uključene u stanični metabolizam (COX-2), prepisivanje (HIF1α), diferencijaciju, prijenos signala i proliferaciju (PAX5 C terminus, FOS, K-RAS). Bolesnici liječeni lenalidomidom/prednizonom praćeni su kroz 2 godine. Izražaja gena pri dijagnozi PMF u odnosu na zdrave ispitanike pokazao je razliku u KS za gene SPARC, K-RAS, CXCR4, PAX5 C terminus, i HIF1α, te za PAX5 C terminus gen u PK. Promjena u izražaju ovih gena uz terapiju nije vidljiva kao niti veza s JAK2 mutacijom. Analiza izražaja stromalnih stanica pokazuje uočljivu razliku.

Abstract (english)

Primary myelofibrosis (PMF) is rare and aggressive myeloproliferative neoplasia. PMF is characterized by bone marrow (BM) fibrosis, leukoerythroblastosis, teardrop poikilocytosis, extramedullary hematopoesis and elevated number of hematopoietic stem CD34+ cells (HSCs) in the peripheral blood (PB). To address if change in expression of HSCs-stromal interacting genes is present, expression of SPARC and CXCR4 were measured in BM and PB mononuclear cells and cultured stromal cells from 32 patients. This investigation also included genes involved in metabolism (COX-2), transcription (HIF1α), differentiation, signaling and proliferation (PAX5 C terminus, FOS, K-RAS). Patients treated with lenalidomide/prednisone were monitored during a 2 year period. Those patients haven’t show any change, but changes in expression are visible for SPARC, K-RAS, CXCR4, PAX5 C terminus and HIF1α gene in BM and PAX5 C terminus in PB compared to healthy individuals. Stromal cells show a wide range of changes.

• Keywords: CD34+stanice; CXCR4; lenalidomid; mikrookoliš; prednizon; primarna mijelofibroza; SPARC
• Keywords (english): CD34+cells; CXCR4; lenalidomide; stroma; prednisone; primary myelofibrosis; SPARC
• Language: croatian
• URN:NBN: urn:nbn:hr:217:181943
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Closed access
• Created on: 2017-05-19 09:18:09