Gatekeeper function of the RUNX1 transcription factor in acute leukemia

Niebuhr, Birte; Fischer, Meike; Täger, Maike; Cammenga, Jörg; Stocking, Carol

doi:10.1016/j.bcmd.2007.07.018

Cited by 34 publications

(35 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…6D). The RUNX1 gene is thought to be involved in normal hematopoiesis and is one of the most frequently disrupted genes in leukemia (Niebuhr et al 2008). These observations support the hypothesis that RUNX1 serves a gatekeeping function for leukemia (Niebuhr et al 2008) and suggest that the pan-leukemic replication-timing fingerprint may be related to the disease state due to an epigenetic phenomenon rather than a mutation or translocation.…”

Section: Deregulation Of Replication Domains In Leukemiamentioning

confidence: 99%

Abnormal developmental control of replication-timing domains in pediatric acute lymphoblastic leukemia

et al. 2012

View full text Add to dashboard Cite

Abnormal replication timing has been observed in cancer but no study has comprehensively evaluated this misregulation. We generated genome-wide replication-timing profiles for pediatric leukemias from 17 patients and three cell lines, as well as normal B and T cells. Nonleukemic EBV-transformed lymphoblastoid cell lines displayed highly stable replicationtiming profiles that were more similar to normal T cells than to leukemias. Leukemias were more similar to each other than to B and T cells but were considerably more heterogeneous than nonleukemic controls. Some differences were patient specific, while others were found in all leukemic samples, potentially representing early epigenetic events. Differences encompassed large segments of chromosomes and included genes implicated in other types of cancer. Remarkably, differences that distinguished leukemias aligned in register to the boundaries of developmentally regulated replicationtiming domains that distinguish normal cell types. Most changes did not coincide with copy-number variation or translocations. However, many of the changes that were associated with translocations in some leukemias were also shared between all leukemic samples independent of the genetic lesion, suggesting that they precede and possibly predispose chromosomes to the translocation. Altogether, our results identify sites of abnormal developmental control of DNA replication in cancer that reveal the significance of replication-timing boundaries to chromosome structure and function and support the replication domain model of replication-timing regulation. They also open new avenues of investigation into the chromosomal basis of cancer and provide a potential novel source of epigenetic cancer biomarkers.

show abstract

Section: Deregulation Of Replication Domains In Leukemiamentioning

confidence: 99%

Abnormal developmental control of replication-timing domains in pediatric acute lymphoblastic leukemia

et al. 2012

View full text Add to dashboard Cite

show abstract

“…The t(8;21) translocation juxtaposes a fragment of the RUNX1 gene with a fragment of the ETO gene on chromosome 8, resulting in the production of a RUNX1-ETO chimeric protein. 1,11 Recently, whole-genome deep sequencing of primary tumor biopsies reveals that RUNX1 is not only commonly mutated in AML, 12,13 but that it is also the most common somatic mutation of the CBF complex in solid tumors, 14,15 suggesting that RUNX1 may normally function as a tumor suppressor gene.…”

mentioning

confidence: 99%

An intragenic long noncoding RNA interacts epigenetically with theRUNX1promoter and enhancer chromatin DNA in hematopoietic malignancies

Wang

Guo

et al. 2014

Int. J. Cancer

View full text Add to dashboard Cite

RUNX1, a master regulator of hematopoiesis, is the most commonly perturbed target of chromosomal abnormalities in hematopoietic malignancies. The t(8;21) translocation is found in 30-40% of cases of acute myeloid leukemia (AML). Recent wholeexome sequencing also reveals mutations and deletions of RUNX1 in some solid tumors. We describe a RUNX1-intragenic long noncoding RNA RUNXOR that is transcribed as unspliced transcript from an upstream overlapping promoter. RUNXOR was upregulated in AML samples and in response to Ara-C treatment in vitro. RUNXOR utilizes its 3 0 -terminal fragment to directly interact with the RUNX1 promoter and enhancers and participates in the orchestration of an intrachromosomal loop. The 3 0 region of RUNXOR also participates in long-range interchromosomal interactions with chromatin regions that are involved in multiple RUNX1 translocations. These data suggest that RUNXOR noncoding RNA may function as a previously unidentified candidate component that is involved in chromosomal translocation in hematopoietic malignancies.

show abstract

“…Ainsi, la translocation t(8 ; 21) (q22 ; q22), associée à environ 15 % des leucé-mies myéloïdes aiguës, affecte le gène RUNX1/AML1 (pour acute myeloid leukaemia 1) qui est essentiel à l'émergence des cellules souches hématopoïétiques et participe à leur différenciation aussi bien dans le lignage myéloïde que dans le lignage lymphoïde [1,11]. …”

unclassified

“…Identification de la calpaïne comme un substrat de AML1-ETO D'autre part, il est apparu que l'expression d'AML1-ETO sous le contrôle des régions régulatrices de LZ provoque la mort des mouches au stade pupe 1 . Ce phénotype nous a servi de base pour la réalisation d'un crible génétique visant à identifier des gènes requis pour l'activité d'AML1-ETO (Figure 2).…”

unclassified

“…Ce phénotype nous a servi de base pour la réalisation d'un crible génétique visant à identifier des gènes requis pour l'activité d'AML1-ETO (Figure 2). Ainsi, sur environ 1 500 gènes ciblés par interférence de 1 Ce stade se situe entre la phase larvaire et la phase adulte. Le stade pupal est marqué par l'épaississement des tégu-ments extérieurs, par l'émergence des cornes antérieures ; à l'issue de se stade s'opère la métamorphose au cours de laquelle la plupart des tissus larvaires sont détruits et remplacés par les tissus adultes.…”

unclassified

See 1 more Smart Citation

La drosophile comme nouveau modèle d’étude des leucémies

et al. 2010

View full text Add to dashboard Cite

> Le développement de leucémies et de lymphomes est souvent associé à des mutations ponctuelles ou à des réarran-gements chromosomiques non aléatoires qui affectent des régulateurs clés du développement hématopoïétique. Ainsi, la translocation t(8 ; 21) (q22 ; q22), associée à environ 15 % des leucé-mies myéloïdes aiguës, affecte le gène RUNX1/AML1 (pour acute myeloid leukaemia 1) qui est essentiel à l'émergence des cellules souches hématopoïétiques et participe à leur différenciation aussi bien dans le lignage myéloïde que dans le lignage lymphoïde [1,11].

show abstract

Gatekeeper function of the RUNX1 transcription factor in acute leukemia

Cited by 34 publications

References 78 publications

Abnormal developmental control of replication-timing domains in pediatric acute lymphoblastic leukemia

Abnormal developmental control of replication-timing domains in pediatric acute lymphoblastic leukemia

An intragenic long noncoding RNA interacts epigenetically with theRUNX1promoter and enhancer chromatin DNA in hematopoietic malignancies

La drosophile comme nouveau modèle d’étude des leucémies

Contact Info

Product

Resources

About