title: Frequent chromatin rearrangements in myelodysplastic syndromes--what stands behind?
abstract: Myelodysplastic syndromes (MDS) represent a clinically and genetically heterogeneous group of clonal haematopoietic diseases characterized by a short survival and high rate of transformation to acute myeloid leukaemia (AML). In spite of this variability, MDS is associated with typical recurrent non-random cytogenetic defects. Chromosomal abnormalities are detected in the malignant bone-marrow cells of approximately 40-80 % of patients with primary or secondary MDS. The most frequent chromosomal rearrangements involve chromosomes 5, 7 and 8. MDS often shows presence of unbalanced chromosomal changes, especially large deletions [del(5), del(7q), del(12p), del(18q), del(20q)] or losses of whole chromosomes (7 and Y). The most typical cytogenetic abnormality is a partial or complete deletion of 5q- that occurs in roughly 30 % of all MDS cases either as the sole abnormality or in combination with other aberrations as a part of frequently complex karyotypes. The mechanisms responsible for the formation of MDS-associated recurrent translocations and complex karyotypes are unknown. Since some of the mentioned aberrations are characteristic for several haematological malignancies, more general cellular conditions could be expected to play a role. In this article, we introduce the most common rearrangements linked to MDS and discuss the potential role of the non-random higher-order chromatin structure in their formation. A contribution of the chromothripsis - a catastrophic event discovered only recently - is considered to explain how complex karyotypes may occur (during a single event).
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v. v. i., Brno, Czech Republic.
authors.forename: E
authors.initials: E
authors.lastname: Pagáčová
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v. v. i., Brno, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Falk
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v. v. i., Brno, Czech Republic.
authors.forename: I
authors.initials: I
authors.lastname: Falková
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v. v. i., Brno, Czech Republic.
authors.forename: E
authors.initials: E
authors.lastname: Lukášová
authors.affiliation: Centre of Oncocytogenetics, General University Hospital in Prague, Prague, Czech Republic, and The Institute of Haematology and Blood Transfusion (IHBT), Prague, Czech Republic.
authors.forename: K
authors.initials: K
authors.lastname: Michalová
authors.affiliation: Department of Internal Medicine - Haematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: A
authors.initials: A
authors.lastname: Oltová
authors.affiliation: Institute of Cellular Biology and Pathology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: I
authors.initials: I
authors.lastname: Raška
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v. v. i., Brno, Czech Republic.
authors.forename: S
authors.initials: S
authors.lastname: Kozubek
mesh_terms: D002843:Chromatin / Q000378:metabolism*; D002869:Chromosome Aberrations; D015321:Gene Rearrangement; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000235:genetics*
chemical_list: D002843:Chromatin