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Calmodulin inhibito...
Calmodulin inhibitors improve erythropoiesis in Diamond-Blackfan anemia
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- Taylor, Alison M. (author)
- Boston Children's Hospital,Harvard University
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- Macari, Elizabeth R. (author)
- Harvard University,Boston Children's Hospital
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- Chan, Iris T. (author)
- Harvard University,Boston Children's Hospital
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- Blair, Megan C. (author)
- Boston Children's Hospital,Harvard University
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- Doulatov, Sergei (author)
- Boston Children's Hospital,Harvard University
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- Vo, Linda T. (author)
- Harvard University,Boston Children's Hospital
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- Raiser, David M. (author)
- Boston Children's Hospital,Harvard University,Brigham and Women's Hospital / Harvard Medical School
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- Siva, Kavitha (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamceller till röda blodkroppar,Forskargrupper vid Lunds universitet,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Stem Cells to Red Blood Cells,Lund University Research Groups
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- Basak, Anindita (author)
- Broad Institute,Boston Children's Hospital,Harvard University
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- Pirouz, Mehdi (author)
- Boston Children's Hospital,Harvard University
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- Shah, Arish N. (author)
- Massachusetts Institute of Technology
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- McGrath, Katherine (author)
- Harvard University,Boston Children's Hospital
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- Humphries, Jessica M. (author)
- Harvard University,Boston Children's Hospital
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- Stillman, Emma (author)
- Harvard University,Boston Children's Hospital
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- Alter, Blanche P. (author)
- National Cancer Institute, USA
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- Calo, Eliezer (author)
- Massachusetts Institute of Technology
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- Gregory, Richard I. (author)
- Harvard University,Boston Children's Hospital
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- Sankaran, Vijay G. (author)
- Broad Institute,Harvard University,Boston Children's Hospital
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- Flygare, Johan (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamceller till röda blodkroppar,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Stem Cells to Red Blood Cells,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Ebert, Benjamin L. (author)
- Boston Children's Hospital,Harvard University,Broad Institute
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- Zhou, Yi (author)
- Harvard University,Boston Children's Hospital
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- Daley, George Q. (author)
- Harvard University,Boston Children's Hospital
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- Zon, Leonard I. (author)
- Boston Children's Hospital,Harvard University,Howard Hughes Medical Institute
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(creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2020
- 2020
- English.
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In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 12:566
- Related links:
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http://dx.doi.org/10...
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https://www.ncbi.nlm...
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https://doi.org/10.1...
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Abstract
Subject headings
Close
- Diamond-Blackfan anemia (DBA) is a rare hematopoietic disease characterized by a block in red cell differentiation. Most DBA cases are caused by mutations in ribosomal proteins and characterized by higher than normal activity of the tumor suppressor p53. Higher p53 activity is thought to contribute to DBA phenotypes by inducing apoptosis during red blood cell differentiation. Currently, there are few therapies available for patients with DBA. We performed a chemical screen using zebrafish ribosomal small subunit protein 29 (rps29) mutant embryos that have a p53-dependent anemia and identified calmodulin inhibitors that rescued the phenotype. Our studies demonstrated that calmodulin inhibitors attenuated p53 protein amount and activity. Treatment with calmodulin inhibitors led to decreased p53 translation and accumulation but does not affect p53 stability. A U.S. Food and Drug Administration-approved calmodulin inhibitor, trifluoperazine, rescued hematopoietic phenotypes of DBA models in vivo in zebrafish and mouse models. In addition, trifluoperazine rescued these phenotypes in human CD34+ hematopoietic stem and progenitor cells. Erythroid differentiation was also improved in CD34+ cells isolated from a patient with DBA. This work uncovers a potential avenue of therapeutic development for patients with DBA.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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To the university's database
- By the author/editor
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Taylor, Alison M ...
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Macari, Elizabet ...
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Chan, Iris T.
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Blair, Megan C.
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Doulatov, Sergei
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Vo, Linda T.
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show more...
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Raiser, David M.
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Siva, Kavitha
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Basak, Anindita
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Pirouz, Mehdi
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Shah, Arish N.
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McGrath, Katheri ...
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Humphries, Jessi ...
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Stillman, Emma
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Alter, Blanche P ...
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Calo, Eliezer
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Gregory, Richard ...
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Sankaran, Vijay ...
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Flygare, Johan
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Ebert, Benjamin ...
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Zhou, Yi
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Daley, George Q.
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Zon, Leonard I.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
- Articles in the publication
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Science Translat ...
- By the university
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Lund University