Chromosomal rearrangements

Flow cytometric evaluation of bone marrow and peripheral blood to characterize the type of leukemia, as well as to detect specific chromosomal rearrangements. The bone marrow at diagnosis usually is hypercellular, with normal hematopoiesis being replaced by leukemic blasts. The presence of greater than 20% blasts in the bone marrow is diagnostic for AML. 

Nadzhafova, R.S., N.S. Bulatova, A.I. Kozlovskii, and I.N. Ryabov. 1994. Identification of a structural chromosomal rearrangement in the karyotype of a root vole from Chernobyl. Russian Jour Genet. 30 318-322... 

Several types of human cancers have been reported to be associated with specific chromosomal rearrangements.)... 

The TK+/ fine was originally isolated as a spontaneously arising revertant clone from a UV-induced TK / clone. The parental TK+/+ cell and the heterozygote were then the only TK-competent mouse lymphoma cells that could be maintained in THMG medium (3 pg ml-1 thymidine, 5 pg ml-1 hypoxanthine, 0.1 pg ml-1 methotrexate and 7.5 pg ml-1 glycine) (Clive, 1987). Thus, like most established lines, these cells are remote from wild-type cells. The karyotype of the TK+/ —3.7.2C line has a modal chromosome number of 40 like wild-type, but has a variety of chromosomal rearrangements and centromeric heteromorphisms (Blazak et al., 1986). 

Since the late 1970s, Southern blot analysis has had greater applicability in linkage analysis and detection of acquired chromosomal rearrangements. Currently, this technique forms the basis of a majority of protocols used in the biopsy... 

Knockout studies in mice revealed that the loss of H2A.X causes an increased frequency of chromosomal rearrangements, which often result in oncogenic transfer-... 

Spectral karyotyping involves the use of five different fluorescent probes that hybridize differentially to different sets of chromosomes. In combination with special cameras and image-pro-cessing software, this technique produces a karyotype in which every chromosome is painted a different color. This aDows the ready visualization of chromosome rearrangements such as small translocations (e.g., the Philadelphia chromosome rearrangement discussed above). 

Chromosomes are highly complex structures that house the genetic material (DNA) of enkaryotic cells. For the most part, chromosomes are reasonably stable strnctnres. Once in a while, this stability is lost and chromosomes rearrange. 

Figure 21.11 Role of p53 as a tumour suppressor gene. p53 induces a cell with damaged DNA either to initiate apoptosis, or arrest the cell cycle, to give time for damaged DNA to be repaired. Damage can be, for example, a mutation, DNA strand breakage or chromosomal rearrangement.

Sadamori N, Miyajima J, Okajima S, et al. 1987. Japanese patients with leukaemia following the use of Thorotrast including a patient with marked chromosomal rearrangements. Acta Haematologica 77 11-14. 

A. Oncogene activation by overexpression, mutation, or chromosomal rearrangement can lead to rapid proliferation of cells and cancer. 

Activation of an oncogene may occur by chromosomal rearrangement creating a dysregulated fusion protein. 

Systematic FISH mapping of disease-associated balanced chromosome rearrangements (Debars) H.-H. Ropers, MPI for Molecular Genetics, Berlin... 

Rowley, J.D. (1984). Biological implications of consistent chromosome rearrangements in leukemia and lymphoma, Cancer Res. 44,3159. 

In acquired malignancies, oncogene activity appears to occur in association with chromosomal rearrangement. There is some evidence that the cooperation of two or more oncogenes, acting in concert, or in sequence, may effect transformation of a normal stale to a malignant one. However, further studies are needed to clarify this siiuation. 

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