Runx2 induces acute myeloid leukemia in cooperation with Cbfβ-SMMHC in mice

Kuo, Ya‐Huei; Zaidi, Sayyed K.; Gornostaeva, Svetlana; Komori, Toshihisa; Stein, Gary S.; Castilla, Lucio H.

doi:10.1182/blood-2008-06-162248

Cited by 77 publications

(70 citation statements)

References 58 publications

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“…This could indicate a specific role for EVI1 overexpression in the development of leukemia in these cases, especially as some of these probe sets included genes that have previously been reported to have a role in hematopoiesis and/or the development of leukemias, for example PBX1 and RUNX2. 33,34 Moreover, recent analysis of the Pbx1 promoter region in mice revealed that Evi-1 upregulates Pbx1 transcription. 50 This emphasizes that PBX1 is a possible target gene of EVI1 involved in the leukemogenesis of EVI1 þ patients.…”

Section: Discussionmentioning

confidence: 99%

EVI1 overexpression in distinct subtypes of pediatric acute myeloid leukemia

et al. 2010

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Overexpression of the ecotropic virus integration-1 (EVI1) gene (EVI1 þ ), localized at chromosome 3q26, is associated with adverse outcome in adult acute myeloid leukemia (AML). In pediatric AML, 3q26 abnormalities are rare, and the role of EVI1 is unknown. We studied 228 pediatric AML samples for EVI1 þ using gene expression profiling and RQ-PCR. EVI1 þ was found in 20/213 (9%) of children with de novo AML, and in 4/8 with secondary AML. It was predominantly found in MLLrearranged AML (13/47), monosomy 7 (2/3), or FAB M6/7 (6/10), and mutually exclusive with core-binding factor AML, t(15;17), and NPM1 mutations. Fluorescent in situ hybridization (FISH) was performed to detect cryptic 3q26 abnormalities. However, none of the EVI1 þ patients harbored structural 3q26 alterations. Although significant differences in 4 years pEFS for EVI1 þ and EVI1À pediatric AML were observed (28%±11 vs 44%±4, P ¼ 0.04), multivariate analysis did not identify EVI1 þ as an independent prognostic factor. We conclude that EVI1 þ can be found in B10% of pediatric AML. Although EVI1 þ was not an independent prognostic factor, it was predominantly found in subtypes of pediatric AML that are related with an intermediate to unfavorable prognosis. Further research should explain the role of EVI1 þ in disease biology in these cases. Remarkably, no 3q26 abnormalities were identified in EVI1 þ pediatric AML.

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Section: Discussionmentioning

confidence: 99%

EVI1 overexpression in distinct subtypes of pediatric acute myeloid leukemia

et al. 2010

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“…Among them, we focused on BCL11A and TRIM24, both of which have been reported to promote p53 degradation either directly or indirectly (23)(24)(25)(26). Moreover, we Since it has been shown that RUNX family members have redundant functions (9,29,30), we sought to examine the expression levels of the other RUNX family members, RUNX2 and RUNX3, in RUNX1-knockdown AML cells. Under our tetracycline-inducible shRNA expression system, the expression levels of RUNX1 started to decline at 24 hours after doxycycline treatment, when the expression levels of RUNX2 and RUNX3 were unchanged.…”

Section: Runx1 Depletion-mediated Antileukemic Effect Requires Functimentioning

confidence: 99%

Genetic regulation of the RUNX transcription factor family has antitumor effects

Morita¹,

Suzuki²,

Maeda³

et al. 2017

Journal of Clinical Investigation

105

192

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“…Below, we focus on Runx1 as the main regulator of hematopoiesis, but also Runx2 and Runx3 express transcripts from 2 promoters to generate alternative isoforms. 94,[111][112][113] Alternative promotor usage contributes to regulatory complexity, with the production of Runx1 transcripts that differ in their 59 and 39 UTRs, their coding sequence, and the time required for their transcription (Figure 3). 46,81,106,114 Differences in the identity and length of the UTRs have been linked to differences in RNA stability and translation efficiency.…”

Section: Structure Of Mammalian Runx Genes and Alternatively Spliced mentioning

confidence: 99%

“…Although Runx2 expression is high in the HSPC compartment of mouse BM, 94 there is no data thus far demonstrating a role for Runx2 in fetal or adult BM HSCs.…”

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confidence: 99%

Runx transcription factors in the development and function of the definitive hematopoietic system

Bruijn

Dzierzak

2017

Blood

148

103

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The Runx family of transcription factors (Runx1, Runx2, and Runx3) are highly conserved and encode proteins involved in a variety of cell lineages, including blood and blood-related cell lineages, during developmental and adult stages of life. They perform activation and repressive functions in the regulation of gene expression. The requirement for Runx1 in the normal hematopoietic development and its dysregulation through chromosomal translocations and loss-of-function mutations as found in acute myeloid leukemias highlight the importance of this transcription factor in the healthy blood system. Whereas another review will focus on the role of Runx factors in leukemias, this review will provide an overview of the normal regulation and function of Runx factors in hematopoiesis and focus particularly on the biological effects of Runx1 in the generation of hematopoietic stem cells. We will present the current knowledge of the structure and regulatory features directing lineage-specific expression of Runx genes, the models of embryonic and adult hematopoietic development that provide information on their function, and some of the mechanisms by which they affect hematopoietic function.

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Runx2 induces acute myeloid leukemia in cooperation with Cbfβ-SMMHC in mice

Cited by 77 publications

References 58 publications

EVI1 overexpression in distinct subtypes of pediatric acute myeloid leukemia

EVI1 overexpression in distinct subtypes of pediatric acute myeloid leukemia

Genetic regulation of the RUNX transcription factor family has antitumor effects

Runx transcription factors in the development and function of the definitive hematopoietic system

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