title: Genomic imbalances in CML blast crisis: 8q24.12-q24.13 segment identified as a common region of over-representation.
abstract: The acute phase of chronic myeloid leukemia (CML) is accompanied by secondary chromosomal changes. The additional changes have a non-random pattern; however, highly abnormal (marker) chromosomes are reported in some 20% of abnormal karyotypes. These marker chromosomes have proved to be beyond the resolution of conventional G-banding analysis. We used molecular cytogenetic techniques to determine the structure of complex chromosome markers in 10 CML-derived cell lines after our investigations of CML patients in blast crisis. Multicolor fluorescence in situ hybridization identified a multitude of structural chromosome aberrations. In addition, genomic gains identified by comparative genomic hybridization (CGH) were mapped to highly complex marker chromosomes in more than one cell line. The most common genomic loss detected by CGH affected chromosome 9, whereas the most common genomic gains affected, in order of frequency, the sequences of 8q, 6, and 13q. The smallest discrete amplification on 8q was identified in cell line MEG-01. This amplicon contains sequences represented by the marker D8S263/RMC08P029 but did not contain the proximal MYC gene or a more distal marker, D8S256/RMC08P025. We determined the size of the amplicon to be less than the chromosome segment 8q24.12-q24.13. The use of region- and locus-specific probes to analyze the organization of highly complex marker structures aided the identification of preferentially amplified genomic regions. The resultant amplifications could harbor gene(s) driving disease progression.
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge, United Kingdom. enacheva@rfc.ucl.ac.uk
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gribble
authors.forename: Alistair G
authors.initials: AG
authors.lastname: Reid
authors.forename: Ian
authors.initials: I
authors.lastname: Roberts
authors.forename: Colin
authors.initials: C
authors.lastname: Grace
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Green
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Nacheva
mesh_terms: D022981:Allelic Imbalance / Q000235:genetics*; D001752:Blast Crisis / Q000235:genetics*; D002869:Chromosome Aberrations; D020223:Chromosome Painting; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005784:Gene Amplification / Q000235:genetics; D015321:Gene Rearrangement / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D020014:K562 Cells; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D009693:Nucleic Acid Hybridization; D014407:Tumor Cells, Cultured
chemical_list: D005819:Genetic Markers