The influence of the cell cycle, differentiation and irradiation on the nuclear location of the abl, bcr and c-myc genes in human leukemic cells

abl and bcr genes play an important role in the diagnostics of chronic myel ogenous leukemia (CML). The translocation of these genes results in an abno rmal chromosome 22 called the Philadelphia chromosome (Ph). The chimeric bc r-abl gene is a fundamental phenomenon in the pathogenesis of CML. Malignan t transformation of hematopoietic cells is also accompanied by the c-myc ge ne changes (translocation, amplification). Nuclear topology of the abl, bcr and c-myc genes was determined in differentiated as well as in irradiated HL-60 cells using dual-colour fluorescence in situ hybridisation and image analysis by means of a high resolution cytometer. After the induction of th e granulocytic differentiation of HL-60 cells with all trans retinoic acid (ATRA) or dimethylsulfoxide (DMSO), the abl and bcr homologous genes were r epositioned closer to the nuclear periphery and the average distances betwe en homologous abl-abl and bcr-bcr genes as well as between heterologous abl -bcr genes were elongated as compared with untreated human leukemic promyel ocytic HL-60 cells, Elongated gene-to-gene and centre-to-gene distances wer e also found for the c-myc gene during granulocytic differentiation. In the case of the monocytic maturation of HL-60 cells treated with phorbol ester s (PMA), the abl and bcr homologous genes were repositioned closer to each other and closer to the nuclear centre. The position of the c-myc gene did not change significantly after the PMA stimulus. The proximity of the abl a nd bcr genes was also found after gamma irradiation using Co-60 (5 Gy). Imm ediately after the gamma irradiation c-myc was repositioned closer to the n uclear centre, but 24 h after radiation exposure the c-myc position returne d back to the pretreatment level. The c-myc gene topology after gamma irrad iation (when the cells are blocked in G(2) phase) was different from that d etected in the G(2) sorted control population. We suggest that changes in t he abl, bcr and c-myc topology in the case of gamma irradiation are not the effects of the cell cycle. It is possible, that differences in the cell cy cle of hematopoietic cells after the gamma irradiation and concurrent proxi mity of the abl, bcr and c-myc genes could be important from the point of v iew of contingent gene translocations, that are responsible for malignant t ransformation of cells. (C) 2000 Elsevier Science Ltd. All rights reserved.