title: Abrogation of RUNX1 gene expression in de novo myelodysplastic syndrome with t(4;21)(q21;q22).
abstract: The disruption of RUNX1 function is one of the main mechanisms of disease observed in hematopoietic malignancies and the description of novel genetic events that lead to a RUNX1 loss of function has been accelerated with the development of genomic technologies. Here we describe the molecular characterization of a new t(4;21)(q21;q22) in a de novo myelodysplastic syndrome that resulted in the deletion of the RUNX1 gene. We demonstrated by quantitative real-time RT-PCR an almost complete depletion of the expression of the RUNX1 gene in our t(4;21) case compared with CD34(+) cells that was independent of mutation or DNA methylation. More importantly, we explored and confirmed the possibility that this abrogation also prevented transactivation of RUNX1 target genes, perhaps confirming the genetic origin of the thrombocytopenia and the myelodysplastic features observed in our patient, and certainly mimicking what has been observed in the presence of the RUNX1/ETO fusion protein.
authors.affiliation: Molecular Cytogenetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre - CNIO, Melchor Fernández Almagro, 3, 28029, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Rio-Machín
authors.forename: Juliane
authors.initials: J
authors.lastname: Menezes
authors.forename: Alba
authors.initials: A
authors.lastname: Maiques-Diaz
authors.forename: Xabier
authors.initials: X
authors.lastname: Agirre
authors.forename: Bibiana I
authors.initials: BI
authors.lastname: Ferreira
authors.forename: Francesco
authors.initials: F
authors.lastname: Acquadro
authors.forename: Sandra
authors.initials: S
authors.lastname: Rodriguez-Perales
authors.forename: Karmele A
authors.initials: KA
authors.lastname: Juaristi
authors.forename: Sara
authors.initials: S
authors.lastname: Alvarez
authors.forename: Juan C
authors.initials: JC
authors.lastname: Cigudosa
mesh_terms: D002871:Chromosome Banding; D002891:Chromosomes, Human, Pair 21; D002894:Chromosomes, Human, Pair 4; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; C082222:RUNX1T1 protein, human; D014157:Transcription Factors
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