Nuclear repositioning of the non-translocated HLXB9 allele in the leukaemia cell line GDM-1 harbouring a t(6;7)(q23;q36)

Abstract

Background/Aims. Transcriptionally active and inactive topologically associated domains (TADs) occupy different areas in the cell nucleus, and chromosomal rearrangements relocating TADs could determine ectopic expression of the repositioned genes. In this study, we investigated the HLXB9 gene in a myeloid leukaemia cell line, GDM-1, known to harbour a rearrangement involving the chromosome 7 with breakpoint distal to HLXB9, highly expressed in these cells. Methods. We used fluorescence in situ hybridisation (FISH) to target the regions involved in the translocation and to distinguish the translocated chromosome from the non-translocated one in interphase nuclei. Results. Two-dimensional (2D) analysis of the interphase FISH data indicated that the two HLXB9 alleles had a different localisation in the cell nuclei, with the translocated allele consistently positioned in the nuclear periphery and the normal one in the more internal portion of the nucleus, known as the transcriptionally active compartment. Conclusion. Our data may indicate that HLXB9 transcripts in GDM-1 cell line do not arise from the allele located in the rearranged chromosome 7, suggesting that regulation of gene expression in cancer cells harbouring chromosomal translocations might be more complex than previously thought, paving the path to further investigations on mechanisms of gene expression.