title: Histone deacetylase in chronic lymphocytic leukemia.
abstract: BACKGROUND
  Elevated histone deacetylase (HDAC) isoenzyme levels have been described in patients with carcinomas and leukemias. HDAC inhibitors (HDACi) have shown promise in the treatment of carcinomas and are currently under intense research. To make better use of HDACi in treating chronic lymphocytic leukemia (CLL), HDAC isoenzyme levels were studied.
  
  
  METHODS
  Quantitative reverse transcriptase polymerase chain reaction for HDAC isoenzyme was measured in 32 patients with CLL and compared with 17 normal volunteer controls. ZAP-70, CD38 and CD44 were also assayed and correlated to HDAC isoenzyme levels.
  
  
  RESULTS
  The results showed: (1) HDAC isoenzyme levels in CLL were significantly increased in class I including HDAC1 and HDAC3, in class II including HADC6, HDAC7, HDAC9 and HDAC10, and in class III including SIRT1 and SIRT6; (2) higher expression of HDAC isoenzyme levels was found in ZAP-70+ compared to ZAP-70- patients, and CD44 expression levels were correlated with HDAC isoenzyme expression levels in the majority of HDAC classes.
  
  
  CONCLUSIONS
  These results suggest: (1) in CLL, elevated HDAC isoenzyme activity is not restricted to one class, and therefore, HDACi therapy may need to be directed to more than one specific class of HDAC; (2) higher HDAC expression activity may indicate a poor prognosis and more advanced disease stage (through indirect evidence), since higher values were found in patients with ZAP-70+ and higher CD44 expression levels.
authors.affiliation: Division of Hematology/Oncology, Brookdale University Hospital Medical Center, Brooklyn, NY 11212, USA. jcwang5@aol.com
authors.forename: J C
authors.initials: JC
authors.lastname: Wang
authors.forename: M I
authors.initials: MI
authors.lastname: Kafeel
authors.forename: B
authors.initials: B
authors.lastname: Avezbakiyev
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: C
authors.initials: C
authors.lastname: Rathnasabapathy
authors.forename: M
authors.initials: M
authors.lastname: Kalavar
authors.forename: Z
authors.initials: Z
authors.lastname: He
authors.forename: J
authors.initials: J
authors.lastname: Burton
authors.forename: S
authors.initials: S
authors.lastname: Lichter
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000368:Aged; D015331:Cohort Studies; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: C497483:CD44 protein, human; D056572:Histone Deacetylase Inhibitors; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D051746:ZAP-70 Protein-Tyrosine Kinase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D006655:Histone Deacetylases