Klonski poremećaji kromosoma i mutacija gena u bolesnika s akutnom mijeloičnom leukemijom

master's thesis

• Title (english): Clonal disorders of chromosomes and gene mutations in patients with acute myeloid leukemia
• Author: Marko Karlović
• Mentor: Slobodanka Ostojić-Kolonić (mentor)
• Committee member: Tomislav Letilović (predsjednik povjerenstva)
• Committee member: Jasenka Markeljević (član povjerenstva)
• Committee member: Slobodanka Ostojić-Kolonić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2021-09-02, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Akutna mijeloična leukemija (AML) najčešća je akutna leukemija u odraslih, a karakterizira ju proliferacija i aberantna diferencijacija mijeloidnih prekursora. Riječ je o vrlo heterogenoj hematološkoj malignosti koja je posljedica različitih kromosomskih abnormalnosti, genskih mutacija te epigenetskih aberacija. Citogenetske abnormalnosti u AML-u uključuju uravnotežene i neuravnotežene translokacije, inverzije, delecije, monosomije, trisomije te složeni kariotip, koji predstavlja najmanje 3 stečene kromosomske aberacije. Citogenetski profil koristi se za raslojavanje bolesnika u povoljnu, srednju i nepovoljnu rizičnu skupinu. Genske mutacije u AML-u javljaju se unutar funkcionalnih kategorija kao što su kinazna signalizacija, tumorski supresori, transkripcijski čimbenici, prekrajanje RNA, kohezin, metilacija DNA te modifikatori kromatina. Prognoza AML-a promjenljiva je ovisno o kliničkim značajkama, kao i genetskim značajkama specifičnim za leukemiju, stoga se genetska karakterizacija određuje u vrijeme dijagnoze, za vrijeme potpune remisije te u relapsu. Genomska heterogenost i složenost unutar AML-a ne omogućuju samo preciznu dijagnozu i prognostičku klasifikaciju, nego, također, i raslojavanje rizika te primjenu personalizirane i ciljane terapije. Kako nova tehnologija napreduje, istraživat će se više mutacija gena, a razvijat će se i nove ciljane terapije koje će u bliskoj budućnosti koristiti većem broju pacijenata s AML-om.

Abstract (english)

Acute myeloid leukemia (AML) is the most common acute leukemia in adults characterized by the proliferation and aberrant differentiation of myeloid precursors. It is a highly heterogeneous hematological malignancy resulting from various chromosomal abnormalities, gene mutations and epigenetic aberrations. Cytogenetic abnormalities in AML include balanced and unbalanced translocations, inversions, deletions, monosomies, trisomies, and complex karyotype representing at least 3 acquired chromosomal aberrations. Cytogenetic profile is used to stratify patients into favorable, intermediate and unfavorable risk group. Gene mutations in AML occur within functional categories such as kinase signaling, tumor suppressors, transcription factors, RNA splicing, cohesin, DNA methylation and chromatin modifiers. The prognosis of AML is variable, based on clinical features, as well as leukemia-specific genetic features. Therefore, genetic characterization is performed at the time of diagnosis, at the time of complete remission, and at the time of relapse. The genomic heterogeneity and complexity within AML not only provide a precise diagnosis and prognostic classification but also risk stratification and an implementation of a personalized and targeted therapy. As the new technology advances, more gene mutations will be explored and new targeted therapies will be developed and benefit more AML patients in the near future.

• Keywords: akutna mijeloična leukemija; kromosomske abnormalnosti; genske mutacije; prognoza; terapija
• Keywords (english): acute myeloid leukemia; chromosomal abnormalities; gene mutations; prognosis; therapy
• Language: croatian
• URN:NBN: urn:nbn:hr:105:995306
• 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: 2022-02-24 10:16:23