title: Preferred co-localization of chromosome 8 and 21 in myeloid bone marrow cells detected by three dimensional molecular cytogenetics.
abstract: The impact of chromosome architecture in the formation of chromosome aberrations is a recent finding of interphase directed molecular cytogenetic studies. Also positive correlation of translocation frequencies and spatial proximity of chromosomes was described. Thus, disease specific chromosomal translocations could be due to tissue specific genomic organization. However, no three-dimensional interphase fluorescence in situ hybridization (FISH) studies for the nuclear architecture of bone marrow (BM) cells have previously been done. In this study, BM of three secondary acute myelogenous leukemia (AML) cases with trisomy 8 and otherwise normal karyotype were evaluated. Bone marrow cells of one AML and one ALL (acute lymphoblastic leukemia) case, peripheral blood lymphocytes and human sperm, all of them with normal karyotype, served as controls. Multicolor banding (MCB) probes for chromosomes 8 and 21 were applied in suspension-FISH (S-FISH). Interestingly, in myeloid bone marrow cells chromosomes 8 (di- and trisomic) and 21 tended to co-localize with their homologue chromosome(s), rather than to be separated. Thus, the co-localization of chromosomes 8 and 21 might promote a translocation providing a selective advantage of t(8;21) cells in AML-M2. In summary, the concept that tissue specific spatial proximity of chromosomes leads to enhanced translocation frequencies was further supported.
authors.affiliation: Jena University Hospital, Institute of Human Genetics and Anthropology, Jena, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Manvelyan
authors.forename: Philipp
authors.initials: P
authors.lastname: Kempf
authors.forename: Anja
authors.initials: A
authors.lastname: Weise
authors.forename: Kristin
authors.initials: K
authors.lastname: Mrasek
authors.forename: Anita
authors.initials: A
authors.lastname: Heller
authors.forename: Amelie
authors.initials: A
authors.lastname: Lier
authors.forename: Klaus
authors.initials: K
authors.lastname: Höffken
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Fricke
authors.forename: Herbert G
authors.initials: HG
authors.lastname: Sayer
authors.forename: Thomas
authors.initials: T
authors.lastname: Liehr
authors.forename: Hasmik
authors.initials: H
authors.lastname: Mkrtchyan
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002891:Chromosomes, Human, Pair 21 / Q000378:metabolism*; D002898:Chromosomes, Human, Pair 8 / Q000378:metabolism*; D020732:Cytogenetic Analysis / Q000379:methods*; D006801:Humans; D017403:In Situ Hybridization; D007399:Interphase; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism*