Differential expression of HDAC3, HDAC7 and HDAC9 is associated with prognosis and survival in childhood acute lymphoblastic leukaemia.
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.
Moreno
Daniel Antunes
DA
Department of Genetics, University of São Paulo, São Paulo, Brazil.
Scrideli
Carlos Alberto
CA
Cortez
Maria Angélica Abdala
MA
de Paula Queiroz
Rosane
R
Valera
Elvis Terci
ET
da Silva Silveira
Vanessa
V
Yunes
José Andres
JA
Brandalise
Silvia Regina
SR
Tone
Luiz Gonzaga
LG
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001853:Bone Marrow / Q000201:enzymology; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006655:Histone Deacetylases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000201:enzymology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016019:Survival Analysis; D000099186:Histone Deacetylase 3
D014408:Biomarkers, Tumor; D006655:Histone Deacetylases; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012097:Repressor Proteins; D000099186:Histone Deacetylase 3; C543273:HDAC7 protein, human; C486544:HDAC9 protein, human