Opredelitev genetskih sprememb v genu PAX5 pri otrocih z akutno limfoblastno levkemijo

Klobučar, Nika (author), Debeljak, Maruša (mentor)

Akutna limfoblastna levkemija (ALL) je najpogostejša vrsta krvnega raka pri otrocih. Raziskave bolnikov z ALL poročajo, da ima skupno 40 % bolnikov z B-celično ALL (B-ALL) spremembe v številu kopij genov, translokacije ali nukleotidne spremembe v genih, ki kodirajo glavne regulatorje razvoja in diferenciacije limfocitov B. Najpogostejša tarča je gen PAX5, ki je spremenjen pri več kot 30 % bolnikov. Z metodo, imenovano sekvenciranje po Sangerju in od ligacije odvisno hkratno pomnoževanje sond (MLPA), smo analizirali maligne celice 68 otrok oz. mladostnikov z B-ALL, ki so se med letoma 2012 in 2019 zdravili na Kliničnem oddelku za otroško hematologijo in onkologijo Pediatrične klinike Univerzitetnega kliničnega centra Ljubljana. Pri 34 % (23) bolnikov smo opredelili spremembo v genu PAX5, natančneje 31 % (21) jih je imelo spremenjeno število kopij gena PAX5, 7 % (5) pa patogeno nukleotidno spremembo. Tri opredeljene spremembe doslej še niso bile opisane: c.1045_1048delCCTC (p.Pro349Serfs), c.101C>T (p.Pro34Leu) in c.197G>A (p.Ser66Asn). Pokazali smo, da so naši rezultati primerljivi z rezultati obsežnejših raziskav iz tujine. Metoda MLPA je pri diagnostiki bolnikov z B-ALL ustrezno orodje za ugotavljanje delecij in duplikacij gena PAX5. Nukleotidne spremembe v genu PAX5 so redkejše od različic v številu kopij.

• Language: Slovenian
• Keywords: B-celična akutna limfoblastna levkemija, gen PAX5, sekvenciranje po Sangerju, od ligacije odvisno hkratno pomnoževanje sond
• Work type: Master's thesis/paper
• Organization: BF - Biotechnical Faculty
• Year: 2021
• PID: 20.500.12556/RUL-127947
• COBISS.SI-ID: 71951363
• Publication date in RUL: 30.06.2021

KLOBUČAR, Nika, 2021, Opredelitev genetskih sprememb v genu PAX5 pri otrocih z akutno limfoblastno levkemijo [online]. Master’s thesis. [Accessed 14 April 2025]. Retrieved from: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=eng&id=127947

Secondary language

• Language: English
• Title: Identification of genetic alterations in the PAX5 gene in children with acute lymphoblastic leukemia

Abstract

Acute lymphoblastic leukemia (ALL) is the most common type of blood cancer in children. Studies of patients with ALL report that a total of 40 % of patients with B cell ALL (B-ALL) have changes in genes copy number, translocations, or nucleotide changes in genes encoding principal regulators of B lymphocyte development and differentiation. The most frequent target is the PAX5 gene, which is altered in more than 30 % of patients. We analysed the malignant cells of 68 children and adolescents with B-ALL who were treated at the Clinical Department of the Pediatric Hematology and Oncology of the Division of Pediatrics, University Medical Centre Ljubljana between 2012 and 2019, using a method called Sanger sequencing and Multiplex ligation-dependent probe amplification (MLPA). A change in the PAX5 gene was identified in 34 % (23) of patients, more precisely 31 % (21) had an altered PAX5 gene copy number, and 7 % (5) had a pathogenic nucleotide change. Three identified changes have not been described so far: c.1045_1048delCCTC (p.Pro349Serfs), c.101C>T (p.Pro34Leu) and c.197G>A (p.Ser66Asn). We have shown that our results are comparable to the results of major research from foreign studies. The MLPA method is an appropriate tool for detecting deletions and duplications of the PAX5 gene in the diagnosis of patients with B-ALL. Nucleotide changes in the PAX5 gene are less common than copy number variants.

• Keywords: B-cell acute lymphoblastic leukemia, PAX5 gene, Sanger sequencing, multiplex ligation dependent probe amplification