Differential expression of HDAC3, HDAC7 and HDAC9 is associated with prognosis and survival in childhood acute lymphoblastic leukaemia

Br J Haematol. 2010 Sep;150(6):665-73. doi: 10.1111/j.1365-2141.2010.08301.x.

Abstract

Altered expression of histone deacetylases (HDACs) is a common feature in several human malignancies and may represent an interesting target for cancer treatment, including haematological malignancies. We evaluated the mRNA gene expression profile of 12 HDAC genes by quantitative real-time polymerase chain reaction in 94 consecutive childhood acute lymphoblastic leukaemia (ALL) samples and its association with clinical/biological features and survival. ALL samples showed higher expression levels of HDAC2, HDAC3, HDAC8, HDAC6 and HDAC7 when compared to normal bone marrow samples. HDAC1 and HDAC4 showed high expression in T-ALL and HDAC5 was highly expressed in B-lineage ALL. Higher than median expression levels of HDAC3 were associated with a significantly lower 5-year event-free survival (EFS) in the overall group of patients (P = 0·03) and in T-ALL patients (P = 0.01). HDAC7 and HADC9 expression levels higher than median were associated with a lower 5-year EFS in the overall group (P = 0.04 and P = 0.003, respectively) and in B-lineage CD10-positive patients (P = 0.009 and P = 0·005, respectively). Our data suggest that higher expression of HDAC7 and HDAC9 is associated with poor prognosis in childhood ALL and could be promising therapeutic targets for the treatment of refractory childhood ALL.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Bone Marrow / enzymology
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Profiling / methods
  • Histone Deacetylases / biosynthesis*
  • Histone Deacetylases / genetics
  • Humans
  • Infant
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / enzymology
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • RNA, Neoplasm
  • Repressor Proteins
  • HDAC7 protein, human
  • HDAC9 protein, human
  • Histone Deacetylases
  • histone deacetylase 3