G1/S transcriptional networks modulated by the HOX11/TLX1 oncogene of T-cell acute lymphoblastic leukemia

Riz, Irene; Hawley, Robert G.

doi:10.1038/sj.onc.1208727

Cited by 42 publications

(66 citation statements)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HOX11 overexpression has previously been implicated in aberrant regulation of both G1/S progression (Riz and Hawley, 2005) in addition to transition into mitosis (Kawabe et al, 1997). Specifically, overexpression of HOX11 in Jurkat T-lymphocyte cell lines leads to aberrant bypass of G2/M arrest induced by ionizing radiation (Kawabe et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Dysregulated expression of mitotic regulators is associated with B-cell lymphomagenesis in HOX11-transgenic mice

et al. 2006

View full text Add to dashboard Cite

Dysregulated expression of the homeobox gene, HOX11 is a frequent etiologic event in T-cell acute lymphoblastic leukemias. HOX11-transgenic mice (IgHl-HOX11 Tg )-expressing HOX11 in the B-cell compartment develop B-cell lymphomas with extended latency. The latency suggests that additional genetic events are required prior to the onset of malignant lymphoma. We report the identification of 17 HOX11 collaborating genes, revealed through their propensity to be targeted in a proviral insertional mutagenesis screen. Seven integrations disrupted genes in mitotic spindle checkpoint control, suggesting that cells with elevated HOX11 expression are especially sensitive to dysregulation of chromosome segregation during mitosis. IgHl-HOX11 Tg primary B-lymphocyte cultures exposed to the aneugenic agents, colchicine and colcemid, exhibited increased incidences of chromosome missegregation as assessed by cytokinesisblock micronucleus assays. Additionally, IgHl-HOX11 Tg cultures were shown to exhibit aberrant bypass of spindle checkpoint arrest, as assessed by the increased presence of cycling cells determined by assessment of DNA content and by BrdU immunolabelling. Western immunoblotting revealed elevated expression of the mitotic effector molecules, cyclin A, cyclin B1 and cdc20 in IgHl-HOX11 Tg cultures. Moreover, spontaneously arising lymphoid neoplasms in IgHl-HOX11 Tg mice frequently exhibit aberrant expression of mitotic regulators, concomitant with increased development of micronuclei, abnormal mitotic checkpoint control and increased incidences of abnormal karyotypes when expanded in culture. Collectively, these findings indicate that abnormal regulation of spindle checkpoint control as a result of HOX11 overexpression leads to a heightened predisposition for development of aneuploidy, contributing to oncogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Dysregulated expression of mitotic regulators is associated with B-cell lymphomagenesis in HOX11-transgenic mice

et al. 2006

View full text Add to dashboard Cite

show abstract

“…The mechanism of synergy between HOX11 overexpression and Ubr1 loss may involve HOX11's role in regulating cell cycle progression. HOX11 overexpression has previously been implicated in aberrant regulation of both G1/S progression (Riz and Hawley, 2005) and transition into mitosis (Kawabe et al, 1997). Recently, we reported that ectopic expression of HOX11 facilitates the ability to aberrantly bypass mitotic arrest induced by aneugenic stress (Chen et al, 2006).…”

Section: /Ubr1mentioning

confidence: 99%

Loss of Ubr1 promotes aneuploidy and accelerates B-cell lymphomagenesis in TLX1/HOX11-transgenic mice

et al. 2006

View full text Add to dashboard Cite

“…The proposed function of HOX11 as a transcriptional regulator is supported by the presence of both a 61-amino acid, helix-turn-helix DNA-binding domain (or homeodomain) and by the localization of the HOX11 protein in the cell nucleus (Neale et al, 1995). HOX11 can also disrupt the G 2 /M cell-cycle checkpoint through a transcription-independent mechanism, which involves its interaction with the PP2A and PP1 phosphatases (Riz and Hawley, 2005;Owens et al, 2006).…”

Section: Aberrant Protein Expression In T-cell Acute Lymphoblastic Lementioning

confidence: 99%

Mechanisms of transcription factor deregulation in lymphoid cell transformation

2007

View full text Add to dashboard Cite

G1/S transcriptional networks modulated by the HOX11/TLX1 oncogene of T-cell acute lymphoblastic leukemia

Cited by 42 publications

References 106 publications

Dysregulated expression of mitotic regulators is associated with B-cell lymphomagenesis in HOX11-transgenic mice

Dysregulated expression of mitotic regulators is associated with B-cell lymphomagenesis in HOX11-transgenic mice

Loss of Ubr1 promotes aneuploidy and accelerates B-cell lymphomagenesis in TLX1/HOX11-transgenic mice

Mechanisms of transcription factor deregulation in lymphoid cell transformation

Contact Info

Product

Resources

About