Correlation of clinical response and response duration with miR-145 induction by lenalidomide in CD34+ cells from patients with del(5q) myelodysplastic syndrome

Cp, Venner; Jw, Woltosz; Tj, Nevill; Deeg, H. Joachim; Cáceres, Gisela; Platzbecker, Uwe; Bl, Scott; Sokol, Lubomir; Sung, Sandy; List, Alan F.; Karsan, Aly

doi:10.3324/haematol.2012.066068

Cited by 30 publications

(33 citation statements)

References 24 publications

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“…Statistically significant increases in miRNA-143 (1.8-fold; P = 0.02) and miRNA-145 (1.9-fold; P = 0.01) expression were observed in del(5q) cells compared with wild-type CD34+ cells; changes in expression correlated with sensitivity to lenalidomide [46]. Furthermore, RNAi knockdown of miRNA-143 and miRNA-145 in healthy cord blood CD34+ cells (thus mimicking haploinsufficiency) conferred sensitivity to lenalidomide.…”

Section: Introductionmentioning

confidence: 99%

Lenalidomide as a disease-modifying agent in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes

et al. 2013

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Deletion of the long arm of chromosome 5, del(5q), is the most prevalent cytogenetic abnormality in patients with myelodysplastic syndromes (MDS). In isolation, it is traditionally associated with favorable prognosis compared with other subtypes of MDS. However, owing to the inherent heterogeneity of the disease, prognosis for patients with del(5q) MDS is highly variable depending on the presence of factors such as additional chromosomal abnormalities, >5 % blasts in the bone marrow (BM), or transfusion dependence. Over recent years, the immunomodulatory drug lenalidomide has demonstrated remarkable efficacy in patients with del(5q) MDS. Advances in the understanding of the pathogenesis of the disease have suggested that lenalidomide targets aberrant signaling pathways caused by haplosufficiency of specific genes in a commonly deleted region on chromosome 5 (e.g., SPARC, RPS14, Cdc25C, and PP2A). As a result, the agent specifically targets del(5q) clones while also promoting erythropoiesis and repopulation of the bone marrow in normal cells. This review discusses recent developments in the understanding of the mechanism of action of lenalidomide, and how this underlies favorable outcomes in patients with del(5q) MDS. In addition, we discuss how improved understanding of the mechanism of disease will facilitate clinicians’ ability to predict/monitor response and identify patients at risk of relapse.

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Section: Introductionmentioning

confidence: 99%

Lenalidomide as a disease-modifying agent in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes

et al. 2013

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“…To determine the effect of miR-143/145 expression on pten-deficient tumors, we knocked down these miRs using a lentiviral miR decoy (sponge) (44). To obtain efficient transduction, tumorspheres derived from 6 independent AMEs were cultured under adherent conditions as monolayer cells, transduced with the lenti-miR-143/145 decoy, sorted for GFP-positive expression, and then subjected to proliferation assays in vitro and/or fat pad engraftment to assess TIC potential in vivo ( Figure 5A).…”

Section: Functional Cooperation Between Mir-143/145 and Pten Loss Promentioning

confidence: 99%

microRNA-143/145 loss induces Ras signaling to promote aggressive Pten-deficient basal-like breast cancer

Wang

Liu

et al. 2017

JCI Insight

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“…There is conflictual evidence as to whether LEN restores expression of RPS14 122 , mir-145 123 degradation, cell cycle reentry, and G2/M arrest of del(5q) cells 124,125 . In keeping with this model, resistance to LEN has been shown to be associated with restoration of P53 accumulation, and ACCEPTED MANUSCRIPT inhibition of TP53 expression by an antisense oligonucleotide modestly enhances del(5q) erythropoiesis 126 .…”

Section: Len In 5q-syndromesmentioning

confidence: 96%

New therapeutic approaches in myelodysplastic syndromes: Hypomethylating agents and lenalidomide

Loiseau¹,

Ali²,

Itzykson³

2015

Experimental Hematology

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Correlation of clinical response and response duration with miR-145 induction by lenalidomide in CD34+ cells from patients with del(5q) myelodysplastic syndrome

Cited by 30 publications

References 24 publications

Lenalidomide as a disease-modifying agent in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes

Lenalidomide as a disease-modifying agent in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes

microRNA-143/145 loss induces Ras signaling to promote aggressive Pten-deficient basal-like breast cancer

New therapeutic approaches in myelodysplastic syndromes: Hypomethylating agents and lenalidomide

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