Deficient Histone Acetylation in Acute Leukemia and the Correction by an Isothiocyanate
Objective: Since histone hypoacetylation due to excess histone deacetylases (HDACs) has been associated with transcriptional repression in leukemia, we aimed to determine deficient histone acetylation in patients with acute leukemia and the effect of its correction by an isothiocyanate. Methods: The...
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| Veröffentlicht in: | Acta haematologica 2010-01, Vol.123 (2), p.71-76 |
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| container_title | Acta haematologica |
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| creator | Xiao, Liyun Huang, Yiqun Zhen, Ruiji Chiao, J.W. Liu, Delong Ma, Xudong |
| description | Objective: Since histone hypoacetylation due to excess histone deacetylases (HDACs) has been associated with transcriptional repression in leukemia, we aimed to determine deficient histone acetylation in patients with acute leukemia and the effect of its correction by an isothiocyanate. Methods: The acetylation status of histones H3 and H4 in cells from patients with untreated acute leukemia was determined by Western blot. Deficient histone acetylation was analyzed in relation to the disease state. Bone marrow cells from 10 patients with acute myeloid leukemia (AML) were cultured in phenylhexyl isothiocyanate (PHI) to evaluate correction of the deficiency. Results: Acetylation of histones H3 and H4 was virtually undetectable or significantly lower in acute leukemia. This deficiency was consistent among all the patients examined. Histone acetylation was up-regulated in the presence of PHI, revealing an excess of deacetylation activity in AML. PHI treatment induced apoptosis, indicating HDAC inhibition was able to correct the deficiency. Conclusions: Deficient histone acetylation may represent an aberration at the epigenetic level in acute leukemia. PHI might represent a target for correcting deficient acetylation, and potential epigenetic regulators for preventing the progression of leukemia. |
| doi_str_mv | 10.1159/000264628 |
| format | Article |
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Methods: The acetylation status of histones H3 and H4 in cells from patients with untreated acute leukemia was determined by Western blot. Deficient histone acetylation was analyzed in relation to the disease state. Bone marrow cells from 10 patients with acute myeloid leukemia (AML) were cultured in phenylhexyl isothiocyanate (PHI) to evaluate correction of the deficiency. Results: Acetylation of histones H3 and H4 was virtually undetectable or significantly lower in acute leukemia. This deficiency was consistent among all the patients examined. Histone acetylation was up-regulated in the presence of PHI, revealing an excess of deacetylation activity in AML. PHI treatment induced apoptosis, indicating HDAC inhibition was able to correct the deficiency. Conclusions: Deficient histone acetylation may represent an aberration at the epigenetic level in acute leukemia. PHI might represent a target for correcting deficient acetylation, and potential epigenetic regulators for preventing the progression of leukemia.</description><identifier>ISSN: 0001-5792</identifier><identifier>EISSN: 1421-9662</identifier><identifier>DOI: 10.1159/000264628</identifier><identifier>PMID: 20051681</identifier><language>eng</language><publisher>Basel, Switzerland</publisher><subject>Acetylation ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Histone Deacetylases - metabolism ; Histones - metabolism ; Humans ; Isothiocyanates - therapeutic use ; Leukemia, Myeloid, Acute - drug therapy ; Leukemia, Myeloid, Acute - metabolism ; Male ; Middle Aged ; Original Paper ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism</subject><ispartof>Acta haematologica, 2010-01, Vol.123 (2), p.71-76</ispartof><rights>2009 S. Karger AG, Basel</rights><rights>Copyright 2009 S. Karger AG, Basel.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-5afe4f3d67092ed4b3a54e9d320173162bd607d22dd8df0c204572606cbe18f43</citedby><cites>FETCH-LOGICAL-c406t-5afe4f3d67092ed4b3a54e9d320173162bd607d22dd8df0c204572606cbe18f43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,2422,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20051681$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xiao, Liyun</creatorcontrib><creatorcontrib>Huang, Yiqun</creatorcontrib><creatorcontrib>Zhen, Ruiji</creatorcontrib><creatorcontrib>Chiao, J.W.</creatorcontrib><creatorcontrib>Liu, Delong</creatorcontrib><creatorcontrib>Ma, Xudong</creatorcontrib><title>Deficient Histone Acetylation in Acute Leukemia and the Correction by an Isothiocyanate</title><title>Acta haematologica</title><addtitle>Acta Haematol</addtitle><description>Objective: Since histone hypoacetylation due to excess histone deacetylases (HDACs) has been associated with transcriptional repression in leukemia, we aimed to determine deficient histone acetylation in patients with acute leukemia and the effect of its correction by an isothiocyanate. Methods: The acetylation status of histones H3 and H4 in cells from patients with untreated acute leukemia was determined by Western blot. Deficient histone acetylation was analyzed in relation to the disease state. Bone marrow cells from 10 patients with acute myeloid leukemia (AML) were cultured in phenylhexyl isothiocyanate (PHI) to evaluate correction of the deficiency. Results: Acetylation of histones H3 and H4 was virtually undetectable or significantly lower in acute leukemia. This deficiency was consistent among all the patients examined. Histone acetylation was up-regulated in the presence of PHI, revealing an excess of deacetylation activity in AML. PHI treatment induced apoptosis, indicating HDAC inhibition was able to correct the deficiency. Conclusions: Deficient histone acetylation may represent an aberration at the epigenetic level in acute leukemia. PHI might represent a target for correcting deficient acetylation, and potential epigenetic regulators for preventing the progression of leukemia.</description><subject>Acetylation</subject><subject>Adult</subject><subject>Aged</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Female</subject><subject>Histone Deacetylases - metabolism</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>Isothiocyanates - therapeutic use</subject><subject>Leukemia, Myeloid, Acute - drug therapy</subject><subject>Leukemia, Myeloid, Acute - metabolism</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Original Paper</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism</subject><issn>0001-5792</issn><issn>1421-9662</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0D1PwzAQBmALgWgpDOwIeUMMAX8kTjJW5aOVKrGAGCPHvlDTJC62M-TfkxIo0-k9PXfDi9AlJXeUJvk9IYSJWLDsCE1pzGiUC8GO0XTY0yhJczZBZ95_DomlPD9FE0ZIQkVGp-j9ASqjDLQBL40PtgU8VxD6WgZjW2zaIXYB8Bq6LTRGYtlqHDaAF9Y5UD-o7IctXnkbNsaqXrYywDk6qWTt4eJ3ztDb0-PrYhmtX55Xi_k6UjERIUpkBXHFtUhJzkDHJZdJDLnmjNCUU8FKLUiqGdM60xVRjMRJygQRqgSaVTGfoZvx787Zrw58KBrjFdS1bMF2vkg5FymjYi9vR6mc9d5BVeycaaTrC0qKfY3FocbBXv9-7coG9EH-9TaAqxFspfsA9w_G-280TXUi</recordid><startdate>20100101</startdate><enddate>20100101</enddate><creator>Xiao, Liyun</creator><creator>Huang, Yiqun</creator><creator>Zhen, Ruiji</creator><creator>Chiao, J.W.</creator><creator>Liu, Delong</creator><creator>Ma, Xudong</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20100101</creationdate><title>Deficient Histone Acetylation in Acute Leukemia and the Correction by an Isothiocyanate</title><author>Xiao, Liyun ; Huang, Yiqun ; Zhen, Ruiji ; Chiao, J.W. ; Liu, Delong ; Ma, Xudong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-5afe4f3d67092ed4b3a54e9d320173162bd607d22dd8df0c204572606cbe18f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Acetylation</topic><topic>Adult</topic><topic>Aged</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Female</topic><topic>Histone Deacetylases - metabolism</topic><topic>Histones - metabolism</topic><topic>Humans</topic><topic>Isothiocyanates - therapeutic use</topic><topic>Leukemia, Myeloid, Acute - drug therapy</topic><topic>Leukemia, Myeloid, Acute - metabolism</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Original Paper</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xiao, Liyun</creatorcontrib><creatorcontrib>Huang, Yiqun</creatorcontrib><creatorcontrib>Zhen, Ruiji</creatorcontrib><creatorcontrib>Chiao, J.W.</creatorcontrib><creatorcontrib>Liu, Delong</creatorcontrib><creatorcontrib>Ma, Xudong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Acta haematologica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xiao, Liyun</au><au>Huang, Yiqun</au><au>Zhen, Ruiji</au><au>Chiao, J.W.</au><au>Liu, Delong</au><au>Ma, Xudong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Deficient Histone Acetylation in Acute Leukemia and the Correction by an Isothiocyanate</atitle><jtitle>Acta haematologica</jtitle><addtitle>Acta Haematol</addtitle><date>2010-01-01</date><risdate>2010</risdate><volume>123</volume><issue>2</issue><spage>71</spage><epage>76</epage><pages>71-76</pages><issn>0001-5792</issn><eissn>1421-9662</eissn><abstract>Objective: Since histone hypoacetylation due to excess histone deacetylases (HDACs) has been associated with transcriptional repression in leukemia, we aimed to determine deficient histone acetylation in patients with acute leukemia and the effect of its correction by an isothiocyanate. Methods: The acetylation status of histones H3 and H4 in cells from patients with untreated acute leukemia was determined by Western blot. Deficient histone acetylation was analyzed in relation to the disease state. Bone marrow cells from 10 patients with acute myeloid leukemia (AML) were cultured in phenylhexyl isothiocyanate (PHI) to evaluate correction of the deficiency. Results: Acetylation of histones H3 and H4 was virtually undetectable or significantly lower in acute leukemia. This deficiency was consistent among all the patients examined. Histone acetylation was up-regulated in the presence of PHI, revealing an excess of deacetylation activity in AML. PHI treatment induced apoptosis, indicating HDAC inhibition was able to correct the deficiency. Conclusions: Deficient histone acetylation may represent an aberration at the epigenetic level in acute leukemia. PHI might represent a target for correcting deficient acetylation, and potential epigenetic regulators for preventing the progression of leukemia.</abstract><cop>Basel, Switzerland</cop><pmid>20051681</pmid><doi>10.1159/000264628</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Acta haematologica, 2010-01, Vol.123 (2), p.71-76 |
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| language | eng |
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| source | MEDLINE; Karger Journals; Alma/SFX Local Collection |
| subjects | Acetylation Adult Aged Child Child, Preschool Female Histone Deacetylases - metabolism Histones - metabolism Humans Isothiocyanates - therapeutic use Leukemia, Myeloid, Acute - drug therapy Leukemia, Myeloid, Acute - metabolism Male Middle Aged Original Paper Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism |
| title | Deficient Histone Acetylation in Acute Leukemia and the Correction by an Isothiocyanate |
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