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Titolo:
The nuclear topography of ABL, BCR, PML, and RAR alpha genes: Evidence forgene proximity in specific phases of the cell cycle and stages of hematopoietic differentiation
Autore:
Neves, H; Ramos, C; da Silva, MG; Parreira, A; Parreira, L;
Indirizzi:
Portuguese Inst Canc, Serv Hematol, Lisbon, Portugal Portuguese Inst CancLisbon Portugal nc, Serv Hematol, Lisbon, Portugal Lisbon Med Sch, Inst Histol & Embryol, Lisbon, Portugal Lisbon Med Sch Lisbon Portugal Inst Histol & Embryol, Lisbon, Portugal
Titolo Testata:
BLOOD
fascicolo: 4, volume: 93, anno: 1999,
pagine: 1197 - 1207
SICI:
0006-4971(19990215)93:4<1197:TNTOAB>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACUTE PROMYELOCYTIC LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; INTERPHASE CHROMOSOMES; IMMUNOGLOBULIN GENES; HUMAN-LYMPHOCYTES; HUMAN CANCER; DNA; ORGANIZATION; REPLICATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Parreira, L Facortugalsboa, Inst Histol & Embriol, Av Prof Egas Moniz, P-1699 Lisbon, P Fac Med Lisboa Av Prof Egas Moniz Lisbon Portugal P-1699 n, P
Citazione:
H. Neves et al., "The nuclear topography of ABL, BCR, PML, and RAR alpha genes: Evidence forgene proximity in specific phases of the cell cycle and stages of hematopoietic differentiation", BLOOD, 93(4), 1999, pp. 1197-1207

Abstract

The mechanisms whereby chromosomal translocations are consistently associated with specific tumor types are largely unknown. A generally accepted hypothesis is that the physical proximity of the involved chromosomal regions may be one important factor in the genesis of these phenomena. Accordingly,a likely possibility is that such a proximity may occur in a cell-lineage and cell-differentiation stage-specific manner. In this work, we have addressed this issue using as models the ABL and BCR genes of t(9;22) and the PML and RAR alpha genes of t(15;17). By using in situ hybridization and confocal microscopy, we have measured the distances between these two pairs of genes in three-dimensionally preserved hematopoietic cells belonging to different cell lineages, at various stages of differentiation, and at various stages of the cell cycle, with the following results. (1) Intergenic distances vary periodically during the cell cycle and a significant association ofABL with BCR and of PML with RAR alpha is seen at the transition between Sand G2, which persists during G2 and prophase (such a behavior is not observed for distances between ABL or PML and the beta-globin genes, used as a control). (2) The proportion of cells in which PML and RAR alpha or ABL andBCR are closely associated is higher in hematopoietic precursors than in B-lymphoid cells (whereas the distances between ABL or PML and the beta-globin genes are not affected by cell type). (3) When intergenic distances in unstimulated bone marrow CD34(+) cells were compared with those in CD34+ cells treated with interleukin-3 (IL-3), a trend towards a higher proximity ofthe ABL and BCR genes in the former and of the PML and RAR alpha genes in the latter is observed. (4) Analysis of B-lymphoid cells during mitosis shows that intergenic distances at metaphase are strongly influenced by physical constraints imposed by the chromosomal location of the gene, by the sizeof the respective chromosome, and by the geometry of the metaphase plate. These findings suggest that intrinsic spatial dynamics, established early in hematopoiesis and perpetuated differentially in distinct cell lineages, may facilitate the collision of individual genes and thus reciprocal recombination between them at subsequent stages of hematopoietic differentiation. (C) 1999 by The American Society of Hematology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 05:31:14