282. Circumventing Hematopoietic Toxicities and Reversing Sickle Phenotype by Lineage-Specific BCL11A Knock Down and γ-Globin Induction
نویسندگان
چکیده
منابع مشابه
Lineage-specific BCL11A knockdown circumvents toxicities and reverses sickle phenotype.
Reducing expression of the fetal hemoglobin (HbF) repressor BCL11A leads to a simultaneous increase in γ-globin expression and reduction in β-globin expression. Thus, there is interest in targeting BCL11A as a treatment for β-hemoglobinopathies, including sickle cell disease (SCD) and β-thalassemia. Here, we found that using optimized shRNAs embedded within an miRNA (shRNAmiR) architecture to a...
متن کاملHydroxyurea down-regulates BCL11A, KLF-1 and MYB through miRNA-mediated actions to induce γ-globin expression: implications for new therapeutic approaches of sickle cell disease
BACKGROUND The major therapeutic benefit of hydroxyurea, the only FDA-approved pharmacologic treatment for sickle cell disease (SCD), is directly related to fetal hemoglobin (HbF) production that leads to significant reduction of morbidity and mortality. However, potential adverse effects such as infertility, susceptibility to infections, or teratogenic effect have been subject of concerns. The...
متن کاملMicroRNA-486-3p Regulates γ-Globin Expression in Human Erythroid Cells by Directly Modulating BCL11A
MicroRNAs (miRNAs) play key roles in modulating a variety of cellular processes through repression of mRNAs target. The functional relevance of microRNAs has been proven in normal and malignant hematopoiesis. While analyzing miRNAs expression profile in unilineage serum-free liquid suspension unilineage cultures of peripheral blood CD34(+) hematopoietic progenitor cells (HPCs) through the eryth...
متن کاملبررسی بیان ژن های موثر در سنتز گاما گلوبین قبل و بعد از تمایز سلول های بنیادی خونساز به رده سلول های اریتروئیدی
Background and aim: Induction of fetal hemoglobin (Hb-F) can improve the patients’ symptoms of haemoglobinopathies. Several factors can induce gamma globin gene expression and increased Hb-F levels in patients. In this study, the expression of genes is involved in regulation of gamma globin synthesis such as PIPKII-alpha BCL11a, and miR-30a during CD34+ hematopoietic stem cell differentiation i...
متن کاملBCL11A mRNA Targeting by miR-210: A Possible Network Regulating γ-Globin Gene Expression
The involvement of microRNAs in the control of repressors of human γ-globin gene transcription has been firmly demonstrated, as described for the miR-486-3p mediated down-regulation of BCL11A. On the other hand, we have reported that miR-210 is involved in erythroid differentiation and, possibly, in γ-globin gene up-regulation. In the present study, we have identified the coding sequence of BCL...
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ژورنال
عنوان ژورنال: Molecular Therapy
سال: 2016
ISSN: 1525-0016
DOI: 10.1016/s1525-0016(16)33091-x