Haploinsufficiency of AML1 Affects the Temporal and Spatial Generation of Hematopoietic Stem Cells in the Mouse Embryo

Cai, Zhongling; Bruijn, Marella de; Ma, Xiaoqian; Dortland, Bjorn; Luteijn, Tanya; Downing, James R.; Dzierzak, Elaine

doi:10.1016/s1074-7613(00)00042-x

Cited by 232 publications

(211 citation statements)

References 40 publications

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“…In the hemogenic arteries (dorsal aorta, vitelline and umbilical) endothelial Runx1 expression precedes the emergence of hematopoietic cells, which has been interpreted as Runx1 marking the hemogenic endothelium. In the absence of Runx1, hemogenic endothelium is still made but no definitive hematopoietic cells are formed [51][52][53][54][55][56]. Deletion of Runx1 in VE-Cadh + cells indicated that Runx1 is critically required in this population [28].…”

Section: Identification Of Hemogenic Endotheliummentioning

confidence: 99%

A short history of hemogenic endothelium

Swiers

Rode

Azzoni

et al. 2013

Blood Cells, Molecules, and Diseases

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Definitive hematopoietic cells are generated de novo during ontogeny from a specialized subset of endothelium, the so-called hemogenic endothelium. In this review we give a brief overview of the identification of hemogenic endothelium, explore its links with the HSC lineage, and summarize recent insights into the nature of hemogenic endothelium and the microenvironmental and intrinsic regulators contributing to its transition into blood. Ultimately, a better understanding of the processes controlling the transition of endothelium into blood will advance the generation and expansion of hematopoietic stem cells for therapeutic purposes.

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Section: Identification Of Hemogenic Endotheliummentioning

confidence: 99%

A short history of hemogenic endothelium

Swiers

Rode

Azzoni

et al. 2013

Blood Cells, Molecules, and Diseases

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show abstract

“…Consistent with this observation, mouse embryos with hemizygosity for the mutant AML1 allele have an increased number of hematopoietic stem cells associated to a decrease in committed progenitors, suggesting that haploinsufficiency of AML1 affects maturation and proliferation of hematopoietic cells. 131 On the other hand, acquired AML1 mutations are observed in 6-10% of sporadic AML and are found at similar frequency in adult and pediatric AML. Mutations are equally distributed between missense and nonsense mutations (resulting in truncated protein) in de novo AML.…”

Section: Aml1mentioning

confidence: 99%

Cooperating gene mutations in acute myeloid leukemia: a review of the literature

et al. 2008

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Acute myeloid leukemia (AML) is a heterogeneous group of neoplastic disorders with great variability in clinical course and response to therapy, as well as in the genetic and molecular basis of the pathology. Major advances in the understanding of leukemogenesis have been made by the characterization and the study of acquired cytogenetic abnormalities, particularly reciprocal translocations observed in AML. Besides these major cytogenetic abnormalities, gene mutations also constitute key events in AML pathogenesis. In this review, we describe the contribution of known gene mutations to the understanding of AML pathogenesis and their clinical significance. To gain more insight in this understanding, we clustered these alterations in three groups: (1) mutations affecting genes that contribute to cell proliferation (FLT3, c-KIT, RAS, protein tyrosine standard phosphatase nonreceptor 11); (2) mutations affecting genes involved in myeloid differentiation (AML1 and CEBPA) and (3) mutations affecting genes implicated in cell cycle regulation or apoptosis (P53, NPM1). This nonexhaustive review aims to show how gene mutations interact with each other, how they contribute to refine prognosis and how they can be useful for risk-adapted therapeutic management of AML patients.

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“…The CBFb subunit is widely expressed (Golling et al, 1996;Ogawa et al, 1993;Wang et al, 1993), whereas AML1 expression during development is limited to hematopoietic stem cells, endothelial cells of the aortagonad-mesonephros, condrogenic centers, olfactory and gustatory mucosa and neural ganglion cells; while after organogenesis it is con®ned to hematopoietic cells (Cai et al, 2000;Corsetti and Calabi, 1997;Simeone et al, 1995).…”

Section: Transcriptional Regulators Involved In Aml-associated Fusionmentioning

confidence: 99%

Common themes in the pathogenesis of acute myeloid leukemia

et al. 2001

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The pathogenesis of acute myeloid leukemia is associated with the appearance of oncogenic fusion proteins generated as a consequence of speci®c chromosome translocations. Of the two components of each fusion protein, one is generally a transcription factor, whereas the other partner is more variable in function, but often involved in the control of cell survival and apoptosis. As a consequence, AML-associated fusion proteins function as aberrant transcriptional regulators that interfere with the process of myeloid di erentiation, determine a stagespeci®c arrest of maturation and enhance cell survival in a cell-type speci®c manner. The abnormal regulation of transcriptional networks occurs through common mechanisms that include recruitment of aberrant corepressor complexes, alterations in chromatin remodeling, and disruption of speci®c subnuclear compartments. The identi®cation and analysis of common and speci®c target genes regulated by AML fusion proteins will be of fundamental importance for the full understanding of acute myeloid leukemogenesis and for the implementation of disease-speci®c drug design. Oncogene (2001) 20, 5680 ± 5694.

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Haploinsufficiency of AML1 Affects the Temporal and Spatial Generation of Hematopoietic Stem Cells in the Mouse Embryo

Cited by 232 publications

References 40 publications

A short history of hemogenic endothelium

A short history of hemogenic endothelium

Cooperating gene mutations in acute myeloid leukemia: a review of the literature

Common themes in the pathogenesis of acute myeloid leukemia

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