Neoangiogeneza i mikrovaskularna gustoća u mijelodisplastičnom sindromu

master's thesis

• Title (english): Neoangiogenesis and microvascular density in myelodysplastic syndrome
• Author: Bruno Novačić
• Mentor: Anita Škrtić (mentor)
• Committee member: Ivana Ilić (predsjednik povjerenstva)
• Committee member: Slavko Gašparov (član povjerenstva)
• Committee member: Anita Škrtić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pathology); Zagreb
• Defense date and country: 2019-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pathology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Clinical Cytology

Abstract

Mijelodisplastični sindromi (MDS) su skupina bolesti monoklonalnih krvotvornih matičnih stanica
obilježenih citopenijom, displazijom u jednoj ili više mijeloičnih loza, neučinkovitom hematopoezom,
rekurentnim genetičkim abnormalnostima i povećanim rizikom od razvoja akutne mijeloične
leukemije. Prema etiologiji MDS se dijeli na primarni koji se pojavljuje de novo i sekundarni koji se
pojavljuje kod osoba koje su liječene kemoterapijom ili su bile izložene zračenju. Dijagnoza MDS-a se
postavlja mikroskopskom analizom aspirata i bioptata koštane srži. Proces angiogeneze sudjeluje i u
patogenezi i tijeku MDS-a, a mikrovaskularna gustoća (MVD) u bioptatima koštane srži jedan je od
prognostičkih čimbenika koji utječe na progresiju MDS-a.
Opći cilj ovoga rada je bilo određivanje učestalosti morfoloških obilježja neoangiogeneze i MVD-a u
bioptatima koštane srži bolesnika oboljelih od MDS-a. Specifični ciljevi su bili usporedba morfoloških
obilježja neoangiogeneze i MVD-a između skupina ispitanika, utvrđivanje korelacije morfometrijskih
varijabli s kliničkopatološkim karakteristikama u MDS-u i određivanje prognostičkoga značaja
morfometrijskih varijabli u skupini bolesnika s MDS-om. U retrospektivnom istraživanju bila su
uključena 44 pacijenta od kojih 32 s MDS-om, 12 s kroničnom mijelomonocitnom leukemijom
(CMML), i 8 ispitanika u kontrolnoj skupini. Skupina bolesnika s MDS-om je imala značajno veći
MVD i najveći dijametar krvnih žila u odnosu na kontrolnu skupinu. Jedina je statistički značajna
razlika u najmanjim dijametrima krvnih žila zabilježena između kontrolne skupine i skupine bolesnika
s CMML-om. Kariotipizirani bolesnici su podijeljeni u prognostičke podskupine prema
Sveobuhvatnom citogenetičkom sustavu bodovanja (CCSS). Analiza varijance (ANOVA) je pokazala
najveću zastupljenost dobre CCSS prognostičke podskupine među bolesnicima s MDS-om. Svim je
bolesnicima izračunata ukupna IPSS-R bodovna vrijednost i proučen daljnji tijek bolesti analizom
podataka o transfuzijskome liječenju, progresiji bolesti i mogućem smrtnom ishodu. Najmanje
polovica bolesnika s MDS-om razvila je potrebu za transfuzijskim liječenjem. Veći udio bolesnika s
progresijom bolesti opažen je u skupinama MDS-a čiji je MVD bio viši. Nije opažena korelacija
najmanjega dijametra krvnih žila i ukupnoga preživljenja bolesnika. Statistički značajne razlike u
vrijednostima MVD-a i morfometrijskih varijabli među skupinama bolesnika s MDS-om upućuju na
izraženiju angiogenezu u koštanoj srži bolesnika s MDS-om višega rizika u odnosu na bolesnike s
MDS-om nižega rizika. Velika mikrovaskularna gustoća i dijametri krvnih žila u skupini bolesnika s
CMML-om ukazuju na angiogeni učinak mijeloproliferativne komponente CMML-a na
mikrovaskulaturu koštane srži.

Abstract (english)

The myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell diseases
characterized by cytopenia, dysplasia in one or more of the major myeloid lineages, ineffective
hematopoiesis, recurrent genetic abnormalities and increased risk of developing acute myeloid
leukemia (AML). Based on etiology, MDS is divided into primary, which occurs de novo, and
secondary, which occurs due to chemotherapy or radiation exposure. MDS is diagnosed by
microscopic examination of bone marrow smear and bone marrow trephine biopsy. The process of
angiogenesis plays a role in the pathogenesis and course of MDS, and microvascular density (MVD)
in bone marrow trephine biopsies is one of prognostic factors which affect MDS progression.
The primary goal of this paper was to determine the frequency of morphological features of
neoangiogenesis and MVD in bone marrow trephine biopsies of patients with MDS. The specific
objectives were to compare the morphological features and MVD among patient groups, to determine correlation of morphometric variables with clinicopathologic characteristics in MDS. This
retrospective research included 44 patients (32 with MDS, 12 with chronic myelomonocytic leukemia
(CMML)) and 8 subjects in control group. MDS group had significantly higher MVD and major axis
values than the control group. The only statistically significant minor axis value difference was
observed between control group and CMML group. Patients with known karyotypes were divided into prognostic subgroups according to the Comprehensive Cytogenetic Scoring System (CCSS). Analysis of variance (ANOVA) showed that the good CCSS prognostic subgroup was the most represented
subgroup among MDS groups. Patients' total IPSS-R score was calculated and information pertaining to patients' transfusion therapy, disease progression and possible fatal outcome was examined. Half of all MDS patients or more eventually required transfusion therapy. MDS groups with higher MVD values showed a higher proportion of patients with disease progression. No correlation was observed between minor axis values and overall patient survival. Statistically significant differences in MVD and morphometric variable values among MDS groups indicate more active angiogenesis in bone marrows of higher risk MDS patients than in bone marrows of lower risk MDS patients. High MVD and major axis values in CMML patients indicate the angiogenic effect of myeloproliferative component of CMML on bone marrow microvascular structures.

• Keywords: angiogeneza; morfometrija; MDS
• Keywords (english): angiogenesis; morphometry; MDS
• Language: croatian
• URN:NBN: urn:nbn:hr:105:033734
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2019-10-17 12:16:14