Identification of novel cytogenetic changes

New molecular cytogenetic techniques now available offer the researcher the ability to analyze cytogenetic changes in much greater detail. In particular, color karyotyping (M-FISH) permits the identification of cryptic translocations not previously detectable by G-banding and also reveals the chromosomal origin of genetic material present in marker chromosomes. Comparative genomic hybridization is a complementary technique which detects quantitative changes (gain or loss of sequences) throughout the genome without the need to obtain metaphase chromosomes. These techniques have been applied to cases of PV with a normal karyotype. However, no cryptic cytogenetic changes have been detected.

Clues about the molecular pathogenesis of the MPDs have also been obtained from the biology of the diseases. Prchal and Axelrad (1974) first demonstrated that erythropoietin (EPO)-independent BFU-E colonies could be grown from PV patients. Spontaneous BFU-E colonies have been observed in the majority of PV patients in addition to a large number of ET patients. Similarly, spontaneous CFU-MEG colony formation occurs, without the addition of exogenous growth factors, in most ET patients. Although it is now believed that progenitors are hypersensitive to a number of growth factors, these results have focussed attention on the EPO and TPO signaling pathway (Figure 9.8).

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