title: Incidence of common preleukemic gene fusions in umbilical cord blood in Slovak population.
abstract: The first event in origination of many childhood leukemias is likely the presence of preleukemic clone (transformed hematopoietic stem/progenitor cells with preleukemic gene fusions (PGF)) in newborn. Thus, the screening of umbilical cord blood (UCB) for PGF may be of high importance for developing strategies for childhood leukemia prevention and treatment. However, the data on incidence of PGF in UCB are contradictive. We have compared multiplex polymerase chain reaction (PCR) and real-time quantitative PCR (RT qPCR) in neonates from Slovak National Birth Cohort. According to multiplex PCR, all 135 screened samples were negative for the most frequent PGF of B-lineage acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). To explore the prevalence of prognostically important TEL-AML1, MLL-AF4 and BCR-ABL (p190), 200 UCB were screened using RT qPCR. The initial screening showed an unexpectedly high incidence of studied PGF. The validation of selected samples in two laboratories confirmed approximately ¼ of UCB positive, resulting in ∼4% incidence of TEL-AML1, ∼6.25% incidence of BCR-ABL1 p190, and ∼0.75% frequency of MLL-AF4. In most cases, the PGF presented at very low level, about 1-5 copies per 105 cells. We hypothesize that low PGF numbers reflect their relatively late origin and are likely to be eliminated in further development while higher number of PGF reflects earlier origination and may represent higher risk for leukemia.
authors.affiliation: Department of Molecular Genetics, Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Škorvaga
authors.affiliation: Department of Molecular Genetics, Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovak Republic; Laboratory of Oncovirology, Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk, Russian Federation.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Nikitina
authors.affiliation: Laboratory of R&D, Eurocord-Slovakia, Bratislava, Slovak Republic.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Kubeš
authors.affiliation: Department of Molecular Genetics, Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Pavol
authors.initials: P
authors.lastname: Košík
authors.affiliation: Department of Molecular Genetics, Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Beata
authors.initials: B
authors.lastname: Gajdošechová
authors.affiliation: Department of Clinical Oncology, National Cancer Institute, Bratislava, Slovak Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Leitnerová
authors.affiliation: Department of Clinical Oncology, National Cancer Institute, Bratislava, Slovak Republic.
authors.forename: Lucia
authors.initials: L
authors.lastname: Copáková
authors.affiliation: Department of Molecular Genetics, Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Igor
authors.initials: I
authors.lastname: Belyaev
mesh_terms: D015331:Cohort Studies; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D005312:Fetal Blood / Q000378:metabolism*; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D050939:Gene Fusion / Q000235:genetics*; D006801:Humans; D007938:Leukemia / Q000175:diagnosis / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011230:Precancerous Conditions / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D018154:Slovakia; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D016044:Fusion Proteins, bcr-abl; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion; C113855:MLL-AF4 fusion protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein