Homeobox Protein HB9 Binds to the Prostaglandin E Receptor 2 Promoter and Inhibits Intracellular cAMP Mobilization in Leukemic Cells

Wildenhain, Sarah; Ingenhag, Deborah; Rückert, Christian; Degistirici, Özer; Dugas, Martin; Meisel, Roland; Hauer, Julia

doi:10.1074/jbc.m111.308965

Cited by 17 publications

(38 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These studies suggested a link between HLXB9 over-expression and leukaemogenesis [ 23 ]. Other authors reported a relatively low HLXB9 expression in normal bone marrow by real time quantitative PCR (RT-Q-PCR) and did not observe HLXB9 expression in healthy CD34-positive bone marrow cells, but described increased levels in the bone marrow of leukaemia patients with the t(7;12) rearrangement [ 6 , 24 ]. Observations from our group and by others confirmed elevated HLXB9 expression in t(7;12) leukaemias as well as in some patients with acute myeloid leukaemia with chromosomal abnormalities other than the t(7;12) [ 20 , 25 ].…”

Section: Reviewmentioning

confidence: 99%

“…These would shed some light on the pathways triggered by this chromosomal rearrangement. The only report to date to explore possible targets for HB9 (the transcription factor coded by the HLXB9 gene) in haematopoietic cells was performed on the HL-60 myeloid cell line using ChiP-on-chip and expression profiling analyses [ 24 ]. This study describes binding of HB9 to the prostaglandin E receptor 2 ( PGTER2 ) promoter resulting in down-regulation of PGTER2 and consequent reduction of intracellular cAMP level.…”

Section: Reviewmentioning

confidence: 99%

“…This down-regulatory effect on PGTER2 expression was also observed in t(7;12) patients. Together with repression of PGTER2 , Wildenhain et al [ 24 ], found that HLXB9 expression in the HL60 cell line had mostly a down-regulatory effect on other genes, particularly ZYX and ETS1 . Physiologically, expression of PGTER2 modulates differentiation of osteoclasts.…”

Section: Reviewmentioning

confidence: 99%

See 2 more Smart Citations

Paediatric acute myeloid leukaemia with the t(7;12)(q36;p13) rearrangement: a review of the biological and clinical management aspects

et al. 2015

View full text Add to dashboard Cite

The presence of chromosomal abnormalities is one of the most important criteria for leukaemia diagnosis and management. Infant leukaemia is a rare disease that affects children in their first year of life. It has been estimated that approximately one third of infants with acute myeloid leukaemia harbour the t(7;12)(q36;p13) rearrangement in their leukaemic blasts. However, the WHO classification of acute myeloid leukaemia does not yet include the t(7;12) as a separate entity among the different genetic subtypes, although the presence of this chromosomal abnormality has been associated with an extremely poor clinical outcome. Currently, there is no consensus treatment for t(7;12) leukaemia patients. However, with the inferior outcome with the standard induction therapy, stem cell transplantation may offer a better chance for disease control. A better insight into the chromosome biology of this entity might shed some light into the pathogenic mechanisms arising from this chromosomal translocation, that at present are not fully understood. Further work is needed to improve our understanding of the molecular and genetic basis of this disorder. This will hopefully open some grounds for possible tailored treatment for this subset of very young patients with inferior disease outcome. This review aims at highlighting the cytogenetic features that characterise the t(7;12) leukaemias for a better detection of the abnormality in the diagnostic setting. We also review treatment and clinical outcome in the cases reported to date.

show abstract

Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

See 1 more Smart Citation

Paediatric acute myeloid leukaemia with the t(7;12)(q36;p13) rearrangement: a review of the biological and clinical management aspects

et al. 2015

View full text Add to dashboard Cite

show abstract

“…ChIP-on-chip studies have been undertaken to explore specific pathways of HLXB9 involvement in order to identify possible targets for this transcription factor [18]. These have shown that the latter binds to the promoter of the prostaglandin E receptor 2 gene ( PTGER2 ) and decreases its expression.…”

Section: Introductionmentioning

confidence: 99%

A Novel Three-Colour Fluorescence in Situ Hybridization Approach for the Detection of t(7;12)(q36;p13) in Acute Myeloid Leukaemia Reveals New Cryptic Three Way Translocation t(7;12;16)

Naiel

Vetter²,

Plekhanova

et al. 2013

Cancers

View full text Add to dashboard Cite

The t(7;12)(q36;p13) translocation is a recurrent chromosome abnormality that involves the ETV6 gene on chromosome 12 and has been identified in 20–30% of infant patients with acute myeloid leukaemia (AML). The detection of t(7;12) rearrangements relies on the use of fluorescence in situ hybridization (FISH) because this translocation is hardly visible by chromosome banding methods. Furthermore, a fusion transcript HLXB9-ETV6 is found in approximately 50% of t(7;12) cases, making the reverse transcription PCR approach not an ideal screening method. Considering the report of few cases of variant translocations harbouring a cryptic t(7;12) rearrangement, we believe that the actual incidence of this abnormality is higher than reported to date. The clinical outcome of t(7;12) patients is believed to be poor, therefore an early and accurate diagnosis is important in the clinical management and treatment. In this study, we have designed and tested a novel three-colour FISH approach that enabled us not only to confirm the presence of the t(7;12) in a number of patients studied previously, but also to identify a cryptic t(7;12) as part of a complex rearrangement. This new approach has proven to be an efficient and reliable method to be used in the diagnostic setting.

show abstract

“…HLXB9 is a gene of 12,801 bp, composed of 3 exons, and the corresponding protein is a transcription factor, HB9, of 401 amino acids [Harrison et al, 1994;Wildenhain et al, 2012]. During development, HB9 controls pancreas and motoneuronal differentiation [Arber et al, 1999;Harrison et al, 1999].…”

Section: Concettamentioning

confidence: 99%

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)

Federico

Leotta²,

Bruno³

et al. 2017

Cytogenet Genome Res

View full text Add to dashboard Cite

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.

show abstract

Homeobox Protein HB9 Binds to the Prostaglandin E Receptor 2 Promoter and Inhibits Intracellular cAMP Mobilization in Leukemic Cells

Cited by 17 publications

References 37 publications

Paediatric acute myeloid leukaemia with the t(7;12)(q36;p13) rearrangement: a review of the biological and clinical management aspects

Paediatric acute myeloid leukaemia with the t(7;12)(q36;p13) rearrangement: a review of the biological and clinical management aspects

A Novel Three-Colour Fluorescence in Situ Hybridization Approach for the Detection of t(7;12)(q36;p13) in Acute Myeloid Leukaemia Reveals New Cryptic Three Way Translocation t(7;12;16)

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)

Contact Info

Product

Resources

About