Ectopic expression of the HLXB9 gene is associated with an altered nuclear position in t(7;12) leukaemias

Ballabio, Erica; Cantarella, Catia Daniela; Federico, Concetta; Mare, Patrizia Di; Hall, Georgina; Harbott, Jochen; Hughes, Jim R.; Saccone, Salvatore; Tosi, Sabrina

doi:10.1038/leu.2009.15

Cited by 40 publications

(97 citation statements)

References 8 publications

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“…The correct maintenance of the higherorder chromatin structure is crucial for cellular health, and its alteration is an emerging factor in human cancer, including leukaemia [Bártová et al, 2000;Ballabio et al, 2009;Tosi et al, 2015]. Over the past decade or so, the observations obtained using microscope imaging and analysis of FISH data were further supported by the introduction of the chromosome conformation capture technique [Dekker et al, 2002] and its variants, such as the high-throughput chromosome conformation capture [Lieberman-Aiden et al, 2009].…”

Section: Concettamentioning

confidence: 90%

“…This chromosomal translocation implied a repositioning of the translocated HLXB9 allele to a more internal area of the cell nucleus, where transcription is generally more active [Ballabio et al, 2009]. Using the myeloid leukaemia-derived cell line GDM-1, also known to overexpress A B Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, ectopic expression of GBX2 has been shown in avian leukaemia, whereas HLXB9 overexpression has been detected in acute myeloid leukaemia (AML) [Deguchi et al, 1993;Kowenz-Leutz et al, 1997;Beverloo et al, 2001]. In particular, overexpression of the HLXB9 gene was found in association with its altered positioning in the nucleus of leukaemic cells carrying the t(7; 12)(q36;p13) rearrangement [Ballabio et al, 2009]. Leukaemia-derived cell lines are a useful tool for the study of genome organisation in relation to gene expression in this pathology.…”

Section: Concettamentioning

confidence: 99%

“…RNL was statistically defined as the median value ± confidence interval of all the analysed hybridisation signals. It was established, analysing a high number of probes [Federico et al, 2008[Federico et al, , 2017Ballabio et al 2009;and own unpublished data], that median values of 0.65 could be considered a landmark between loci located at the nuclear periphery and at the nuclear interior. Differences in RNLs were statistically evaluated by 2-tailed t test.…”

Section: Radial Nuclear Location Analysismentioning

confidence: 99%

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Nuclear Repositioning of the Non-Translocated HLXB9 Allele in the Leukaemia Cell Line GDM-1 Harbouring a t(6;7)(q23;q36)

Federico

Leotta²,

Bruno³

et al. 2017

Cytogenet Genome Res

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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 chromosome 7 with a breakpoint distal to HLXB9, highly expressed in these cells. We used FISH to target the regions involved in the translocation and to distinguish the translocated chromosome from the non-translocated one in interphase nuclei. Two-dimensional analysis of the interphase FISH data indicated that the 2 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. Our data may indicate that HLXB9 transcripts in the GDM-1 cell line do not arise from the allele located in 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.

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Section: Concettamentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Concettamentioning

confidence: 99%

Section: Radial Nuclear Location Analysismentioning

confidence: 99%

See 2 more Smart Citations

Nuclear Repositioning of the Non-Translocated HLXB9 Allele in the Leukaemia Cell Line GDM-1 Harbouring a t(6;7)(q23;q36)

Federico

Leotta²,

Bruno³

et al. 2017

Cytogenet Genome Res

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“…A fusion transcript arising from the t(7;12) rearrangement has been described as the HLXB9-ETV6 fusion [8]. However, this fusion transcript has been identified in only approximately 50% of cases harbouring the t(7;12)(q36;p13) [6,9]. Therefore, a more reliable method must be used for the detection of this rearrangement.…”

Section: Introductionmentioning

confidence: 99%

Detection of t(7;12)(q36;p13) in paediatric leukaemia using dual colour fluorescence in situ hybridisation

Owoka¹,

Vetter²,

Federico³

et al. 2015

Hematol Leuk

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The identification of chromosomal rearrangements is of utmost importance for the diagnosis and classification of specific leukaemia subtypes and therefore has an impact on therapy choices in individual cases. The t(7;12)(q36;p13) is a cryptic rearrangement that is difficult to recognise using conventional cytogenetic methods and is often undetected by reverse transcription polymerase chain reaction due to the absence of a fusion transcript in many cases. Here we present a reliable and easy to use dual colour fluorescence in situ hybridisation assay for the detection of the t(7;12)(q36;p13) rearrangement. A comparison with previous similar work is given and advantages and limitations of this novel approach are discussed.

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Acute myeloid leukaemia

Smith¹,

McKerrell²

2016

The Genetic Basis of Haematological Cancers

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Ectopic expression of the HLXB9 gene is associated with an altered nuclear position in t(7;12) leukaemias

Cited by 40 publications

References 8 publications

Nuclear Repositioning of the Non-Translocated <b><i>HLXB9</i></b> Allele in the Leukaemia Cell Line GDM-1 Harbouring a t(6;7)(q23;q36)

Nuclear Repositioning of the Non-Translocated <b><i>HLXB9</i></b> Allele in the Leukaemia Cell Line GDM-1 Harbouring a t(6;7)(q23;q36)

Detection of t(7;12)(q36;p13) in paediatric leukaemia using dual colour fluorescence in situ hybridisation

Acute myeloid leukaemia

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