Location and function of critical genes in leukemogenesis inferred from cytogenetic abnormalities in hematologic malignancies.
Dramatic advances in the cytogenetic analysis of chromosomal rearrangements of hematopoietic malignancies have occurred over the past years. These are due to considerable improvement in the techniques of molecular cytogenetics. Various applications of fluorescence in situ hybridization (FISH), used in conjunction with conventional cytogenetics, make the recognition of some abnormalities easier, and the localization of chromosomal breakpoints in structural rearrangements more precise. Under many circumstances, accurate breakpoint localization is the first step toward the identification of genes involved in translocations and inversions. Some of the genes recently discovered may be rearranged with several partner genes. These promiscuous genes are natural experiments that generate mutants which help to identify the function of genes rearranged in hematopoietic malignancies as well as that of their normal counterparts. The diversity of the genes implicated in leukemogenesis makes their functional study a challenge, but, as recently shown by their role in chromatin remodeling, increasing recognition of cross-talk between many of these genes justifies the development of analyses of leukemia-associated chromosome abnormalities and of their functional consequences.
Bernard
O A
OA
INSERM U434, Institut de Génétique Moléculaire, Paris, France.
Berger
R
R
D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D020732:Cytogenetic Analysis; D015321:Gene Rearrangement; D019337:Hematologic Neoplasms / Q000235:genetics*; D006801:Humans; D007938:Leukemia / Q000235:genetics