ULOGA EKSPRESIJE RECEPTORA NOTCH1 I LIGANADA JAGGED1 I DLL1 U KRVOTVORNIM MATIČNIM STANICAMA MIKROOKOLIŠA MULTIPLOGA MIJELOMA

doctoral thesis

• Title (english): THE ROLE OF NOTCH1 RECEPTOR, JAGGED1 AND DLL1 LIGAND EXPRESSION IN HEMATOPOIETIC STEM CELLS OF THE MICROENVIRONMENT IN MULTIPLE MYELOMA
• Author: Silvana Jurenec
• Mentor: Anita Škrtić (mentor)
• Mentor: Mariastefania Antica (komentor)
• Committee member: Delfa Radić Krišto (predsjednik povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Sanja Kapitanović (član povjerenstva)
• Committee member: Petra Korać (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-09-29, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 577 - Biochemistry. Molecular biology. Biophysics

Abstract

Signalni put Notch u krvotvornim matičnim stanicama (KMS) koštane srži (KS) multiplog
mijeloma (MM) analiziran je kroz ekspresiju proteina NOTCH1, JAGGED1, DLL1 u KMS
imunofenotipizacijom, u tumorskim plazma stanicama (TPS) imunohistokemijskim bojenjem, uz
analizu citogenetičkih promjena visokog rizika (CGVR) u TPS metodom FISH te analizu
histoloških promjena u koštanoj srži MM. Ekspresija JAGGED1 i DLL1 u KMS značajno je niža
u MM nego u zdravih darivatelja. Prisutna je negativna korelacija između ekspresije NOTCH1 i
JAGGED1 u KMS MM, a pozitivna korelacija između ekspresije NOTCH1 i liganada
JAGGED1 i DLL1 u TPS. U TPS s prisutnom barem jednom CGVR i difuznim infiltratom KS
značajno je veća razina ekspresije NOTCH1 i JAGGED1 i intenziteta ekspresije NOTCH1.
Potvrđena je hipoteza da postoji razlika u ekspresiji JAGGED1 i DLL1 u KMS u MM i zdravoj
KS, no nije dokazana povezanost ekspresije NOTCH1, JAGGED1, DLL1 u KMS i TPS u MM.
Povezanost ekspresije NOTCH1, JAGGED1 i DLL1 u istoj vrsti stanica ukazuje na razliku u
homotipnoj i heterotipnoj staničnoj signalizaciji puta Notch u MM.

Abstract (english)

The Notch signaling pathway in hematopoietic stem cells (HSC) in the multiple myeloma (MM)
bone marrow (BM) was analyzed with the NOTCH1, JAGGED1, DLL1 expression in HSC by
immunophenotyping and in tumor plasma cells (TPC) by immunohistochemical staining. High
risk cytogenetic changes (CGHR) using the FISH method and histological analysis of TPC in the
BM MM was performed. JAGGED1 and DLL1 expression in HSC were significantly lower in
MM than in healthy donors. There was a negative correlation between NOTCH1 and JAGGED1
expression in HSC MM, and a positive correlation between NOTCH1 and JAGGED1 and DLL1
in TPC, respectively. In TPC with at least one CGHR present and a BM diffuse infiltrate, the
NOTCH1 and JAGGED1 expression and the intensity of NOTCH1 expression were significantly
higher. The hypothesis that there is a difference in the expression of JAGGED1 and DLL1 in
HSC between MM and healthy BM was confirmed, but the correlation of the NOTCH1,
JAGGED1, DLL1 expression in HSC and TPC in MM was not proven. The association of
NOTCH1, JAGGED1 and DLL1 expression in the same cell type indicates a difference in
homotypic and heterotypic cellular signaling of the Notch pathway in MM.

• Keywords: NOTCH1; JAGGED1; DLL1; krvotvorna matična stanica; multipli mijelom
• Keywords (english): NOTCH1; JAGGED1; DLL1; hematopoietic stem cell; multiple myeloma
• Language: croatian
• URN:NBN: urn:nbn:hr:217:592012
• Promotion: 2023
• Project: Number: IP-2020-02-2431; Title: Obnova timusa za preciznu medicinu u liječenju tumora i leukemija; Title: Thymus renewal for precision medicine in cancer and leukaemia treatment; Acronym: THYMINNOVA; Leader: Mariastefania Antica; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• Study programme: Title: Doctoral study; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti u području prirodnih znanosti (doktor/doktorica znanosti u području prirodnih znanosti)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-10-25 09:12:39