Promjena lokusa 11q23/MLL u bolesnika s akutnom mijeloičnom leukemijom

master's thesis

• Title (english): Change in 11q23/MLL locus in patients with acute myeloid leukemia
• Author: Adriana Bobinec
• Mentor: Sanja Davidović-Mrsić (mentor)
• Mentor: Inga Marijanović (mentor)
• Committee member: Inga Marijanović (predsjednik povjerenstva)
• Committee member: Sanja Davidović-Mrsić (član povjerenstva)
• Committee member: Dubravka Hranilović (član povjerenstva)
• Committee member: Mirjana Kalafatić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2013-02-25, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Akutna mijeloična leukemija (AML) je klonalni poremećaj uzrokovan malignom transformacijom hematopoetske matične stanice u koštanoj srži. Ukoliko se ne liječi uzrokuje smrt zbog abnormalne hematopoeze i pretjeranog stvaranja nezrelih krvnih stanica (blasta). Mutacije koje uzrokuju AML uglavnom zahvaćaju gene koji kodiraju proteine uključene u signalne puteve, transkripcijske faktore i epigenetičke regulatore s različitom prognozom bolesti ovisno o vrsti stečenih kromosomskih promjena. Lokus 11q23 kodira gen MLL (mixed lineage leukemia), ortolog tritoraks gena kod vinske mušice (Drosophila melanogaster), koji ima ulogu transkripcijskog faktora i regulatora gena HOX. Do sada je otkriveno 85 različitih translokacija koje zahvaćaju ovaj gen te 66 partnerskih gena s kojima MLL stvara fuzije. Promjene lokusa 11q23/MLL klinički imaju vrlo lošu prognozu. Cilj je bio detektirati i opisati specifične promjene gena MLL metodom interfaznog FISH-a i klasičnom citogenetičkom analizom u AML pozitivnih ispitanika. Rezultati su pokazali da je korištenjem jedne specifične FISH probe (Vysis) moguće detektirati različite promjene lokusa MLL. Metoda I- FISH-a se pokazala nezamjenjivom u dijagnosticiranju promjena gena MLL koje nije bilo moguće detektirati klasičnom citogenetičkom analizom. Pokazalo se da su translokacije najučestalija genska promjena lokusa MLL, te da preuredba gena MLL ima najveću incidenciju u podtipu AML-M5b prema FAB klasifikaciji AML.

Abstract (english)

Acute myeloid leukemia (AML) is a clonal disorder caused by malignant transformation of hematopoietic stem cells in bone marrow. Untreated illness causes death due to abnormal hematopoesis and overproduction of undifferentiated cells (blasts). Mutations causing AML mainly occur in genes coding for signaling pathway proteins, transcription factors and epigenetic regulators with varying clinical outcome depending on types of acquired chromosomal abnormalities. Locus 11q23 codes for MLL (mixed lineage leukemia) gene, ortholog of trithorax protein in fruitfly (Drosophila melanogaster), which is a transcription factor and regulator of HOX genes. So far it has been found that MLL gene is involved in 85 different translocations and that it forms 66 fusions with various partner genes. Changes of 11q23/MLL locus have been associated with very poor clinical outcome. The goal was to detect and describe specific changes of MLL gene in AML positive patients using interphase FISH method as well as classical cytogenetic analysis. Results showed that different changes of MLL locus can be detected using one locus specific probe (Vysis). I-FISH method proved to be indispensable in diagnosis of MLL gene changes that could not be detected using classical cytogenetic analysis. Translocations were found to be the most common chromosomal alterations associated with MLL locus. It was also found that MLL rearrangement has the highest incidence in AML-M5b subtype based on FAB classification of AML.

• Keywords: AML; fuzije MLL; metoda I-FISH; podjela FAB
• Keywords (english): AML; MLL fusions; I-FISH method; FAB classification
• Language: croatian
• URN:NBN: urn:nbn:hr:217:962513
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2017-04-25 12:12:27