Common deleted genes in the 5q− syndrome: thrombocytopenia and reduced erythroid colony formation in SPARC null mice

Lehmann, Sören; O’Kelly, James; Raynaud, Sophie; Funk, Sarah E.; Sage, E. Helene; Koeffler, H. Phillip

doi:10.1038/sj.leu.2404852

Cited by 64 publications

(55 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The commonly deleted region (CDR) at 5q32 contains 40 genes and several of them may be implicated in hematopoiesis; however, none of the genes seem to be responsible for all characteristics of 5qÀ syndrome. [30][31][32] Three miRNAs (miR-143, miR-145 and miR-378) are mapped within the region and miR-146a is located in its proximity. Expression of these miRNAs was examined by Starczynowski et al 33 who showed correlation between del(5q) and the loss of miR-145 and miR-146a in a murine model.…”

Section: Discussionmentioning

confidence: 99%

Distinctive microRNA expression profiles in CD34+ bone marrow cells from patients with myelodysplastic syndrome

et al. 2010

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are small non-coding RNAs functioning as regulators of hematopoiesis. Their differential expression patterns have been linked with various pathological processes originating from hematopoietic stem cells (HSCs). However, limited information is available regarding the role of miRNAs in myelodysplastic syndrome (MDS). Using miRNA arrays, we measured expression of 1,145 miRNAs in CD34+ bone marrow cells obtained from 39 MDS and acute myeloid leukemia (AML) evolved from MDS patients, and compared them with those of six healthy donors. Differential miRNA expression was analyzed and a panel of upregulated (n¼13) and downregulated (n¼9) miRNAs were found (Po0.001) in MDS/AML patients. An increased expression of a large miRNA cluster mapped within the 14q32 locus was detected. Differences in miRNA expression of MDS subtypes showed a distinction between early and advanced MDS; an apparent dissimilarity was observed between RAEB-1 and RAEB-2 subtypes. In early MDS, we monitored upregulation of proapoptotic miR-34a, which may contribute to the increased apoptosis of HSCs. Patients with 5q deletion were characterized by decreased levels of miR-143* and miR-378 mapped within the commonly deleted region at 5q32. This is an early report describing differential expression in MDS CD34+ cells, likely reflecting their disease-specific regulation.

show abstract

Section: Discussionmentioning

confidence: 99%

Distinctive microRNA expression profiles in CD34+ bone marrow cells from patients with myelodysplastic syndrome

et al. 2010

View full text Add to dashboard Cite

show abstract

“…RPS14 is an essential component of the 40S ribosome. Consistent with tumor-suppressor function, RPS14 gene (5q33.1) expression is diminished in (del)5 or 5q-MDS patients (Boultwood et al, 2007;Lehmann et al, 2007;Ebert et al, 2008;Pellagatti et al, 2008;Valencia et al, 2008), and RPS14 re-expression in CD34 þ HSCs from affected patients slows proliferation and rescues protein synthesis defects (Ebert et al, 2008). It is noted that, Diamond-Blackfan anemia, which shares several clinical features with MDS, is characterized by loss-of-function mutations or deletion of the ribosomal components, RPS19, RPS24, RPS17 and RPL35A (Gazda et al, 2006;Cmejla et al, 2007;Farrar et al, 2008;Shannon and Le Beau, 2008).…”

Section: Rps14: a Role For Defective Translation In Mds?mentioning

confidence: 92%

5q– myelodysplastic syndromes: chromosome 5q genes direct a tumor-suppression network sensing actin dynamics

et al. 2009

View full text Add to dashboard Cite

“…16 Because deletion of 5q represents the major cytogenetic abnormality associated with MDS, it has been hypothesized that this region may contain an important MDS suppressor gene. 16,18 One such candidate is the NPM (Nucleophosmin) gene, located in the 5q region. Mutations of the NPM1 gene have also been found in 4.4% of MDS patients.…”

Section: Mds Mouse Models Of Chromosomal Deletions: Candidate Genes Fmentioning

confidence: 99%

Engineering mouse models with myelodysplastic syndrome human candidate genes; how relevant are they?

2012

View full text Add to dashboard Cite

Myelodysplastic syndromes represent particularly challenging hematologic malignancies that arise from a large spectrum of genetic events resulting in a disease characterized by a range of different presentations and outcomes. Despite efforts to classify and identify the key genetic events, little improvement has been made in therapies that will increase patient survival. Animal models represent powerful tools to model and study human diseases and are useful pre-clinical platforms. In addition to enforced expression of candidate oncogenes, gene inactivation has allowed the consequences of the genetic effects of human myelodysplastic syndrome to be studied in mice. This review aims to examine the animal models expressing myelodysplastic syndrome-associated genes that are currently available and to highlight the most appropriate model to phenocopy myelodysplastic syndrome disease and its risk of transformation to acute myelogenous leukemia. ©2013 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol.2012.069385 ABSTRACTMouse models myelodysplastic syndrome human candidate genes haematologica | 2013; 98 (1) 11 Figure 1. Mouse models to study malignant hematologic disease. Several strategies can be employed to create mouse models of disease. Candidate genes can be introduced into the germline under the control of appropriate promoters to drive expression in certain cell compartments. Knock-out strategies create gene deficient mice, whilst knock-in strategies use the endogenous promoters; but again these tend to be conditional systems requiring specific promoters to determine in which cell the genes are introduced. Transduction of bone marrow and reinfusion is a powerful tool. Xenograft models are theoretically the best if the techniques involved can be improved.

show abstract

Common deleted genes in the 5q− syndrome: thrombocytopenia and reduced erythroid colony formation in SPARC null mice

Cited by 64 publications

References 30 publications

Distinctive microRNA expression profiles in CD34+ bone marrow cells from patients with myelodysplastic syndrome

Distinctive microRNA expression profiles in CD34+ bone marrow cells from patients with myelodysplastic syndrome

5q– myelodysplastic syndromes: chromosome 5q genes direct a tumor-suppression network sensing actin dynamics

Engineering mouse models with myelodysplastic syndrome human candidate genes; how relevant are they?

Contact Info

Product

Resources

About