Inactivation of HDAC1 or HDAC2 induces gamma globin expression without altering cell cycle or proliferation. Issue 7 (28th May 2015)

• Record Type: Journal Article
• Authors: Esrick, Erica B.; McConkey, Marie; Lin, Katherine; Frisbee, Alyse; Ebert, Benjamin L.
• Is Part Of: American journal of hematology. Volume 90:Issue 7(2015:Jul.)
• Page Start: 624
• Page End: 628
• Publication Date: 2015-05-28
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.24019
• Languages: English
• ISSNs: 0361-8609

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Other than hydroxyurea, no pharmacologic agents are clinically available for fetal hemoglobin (HbF) induction in sickle cell disease (SCD). An optimal candidate would induce HbF without causing cell cycle inhibition and would act independently of hydroxyurea in order to yield additional HbF induction when combined. We explored whether inhibition of histone deacetylase (HDAC) 1 or HDAC2 could achieve these goals. In human erythroid progenitor cells, shRNA knockdown of the <italic>HDAC1</italic> or <italic>HDAC2</italic> genes induced gamma globin, without altering cellular proliferation <italic>in vitro</italic>, and without altering cell cycle phase. Treatment with hydroxyurea in combination with <italic>HDAC2</italic> knockdown yielded a further increase in gamma globin expression. Additionally, when CD34+ cells were treated with both hydroxyurea and MS‐275 (an inhibitor of HDAC 1, 2, and 3), an additive induction of relative gamma globin expression was achieved. Our findings support further clinical investigation of HDAC inhibitors in combination with hydroxyurea in SCD patients. Am. J. Hematol. 90:624–628, 2015. © 2015 Wiley Periodicals, Inc.</p> </abstract>