Naslov
Microsatellite instability and loss of heterozygosity in patients diagnosed with chronic myeloid leukaemia

Autori
Laslo, Dorian ; Žebčević, Dario, Periša, Vlatka ; Štefanić, Mario ; Tokić, Stana

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, pp prezentacija, znanstveni

Izvornik
OSCON 2021 Book of Abstracts / Pavlović, Vedrana - Osijek : J.J.Strossmayer University of Osijek, Faculty of Medicine, 2021, 79-79

ISBN
978-953-7736-48-4

Skup
3rd International Translational Medicine Congress of Students and Young Physicians (OSCON 2021)

Mjesto i datum
Osijek, Hrvatska, 19.03.2021. - 20.03.2021

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
microsatellite ; BCR-ABL1 ; CML

Sažetak
Introduction: Philadelphia-positive chronic myeloid leukemia (CML) is a clonal myeloproliferative disease driven by t(9 ; 22) (q34 ; q11) chromosomal translocation that gives rise to a druggable, constitutively active tyrosine kinase BCR-ABL1. As the disease progresses, the surviving pool of self-renewing leukemic stem cells continues to accumulate mutational events that end-up in a widespread loss of heterozygosity (LOH) and microsatellite instability (MSI). In solid cancer, these processes have been associated with treatment failure and poor prognosis, but less is known about the prevalence and impact of MSI and LOH in CML. Materials and methods: Paired buccal swabs and peripheral blood samples were collected from 10 healthy volunteers and 18 Ph(+)CML patients with one (n=13) or two (n=5) prior TKIs and evidence of complete cytogenetic response. Poly- and mononuclear leukocytes were separated via gradient centrifugation, and QlAmp DNA Blood Midi set/InstaGene Matrix were used for DNA extraction. DNA was quantified (Qubit fluorometer), and 15 somatic short tandem repeats (STR) were analyzed by capillary electrophoresis (AmpFLSTR Identifiler Plus PCR Amplification set). Results: MSI events were encountered in 4 out of 18 CML patients, including 2 individuals who switched from imatinib to second-generation TKI (nilotinib). The highest MSI occurrence was noticed in polymorphonuclears (17 %), most often within D8S1179 (n=3), D3S1358 (n=2), and D5S818 (n=2) loci. No MSI was observed in buccal swabs representing germline STR content in either group. Conclusion: MSI is unfrequent in CML, at least in the initial, therapeutically amenable stage. High-coverage whole-genome sequencing is needed to address genetic instabilities in stable and accelerated CML.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA