The expression of histone deacetylase 4 is associated with prednisone poor-response in childhood acute lymphoblastic leukemia.
This study aimed at the identification of histone deacetylase (HDAC) isoforms relevant for childhood acute lymphoblastic leukemia (ALL). Expression of HDAC1-11 was determined in 93 primary ALL and eight healthy donor samples. HDAC1, HDAC2 and HDAC8 showed significantly higher expressions in ALL samples. Correlation analysis of HDAC expression with clinicopathological parameters revealed that high HDAC1, HDAC2, HDAC4 and HDAC11 levels were significantly associated with unfavorable prognostic factors. Particularly, high HDAC4 expression was associated with high initial leukocyte count, T cell ALL and prednisone poor-response. siRNA-mediated inhibition of HDAC4 sensitized a T-ALL cell line to etoposide-induced cell death. In conclusion, our data point to HDAC4 as drug target in childhood ALL, especially in prednisone poor-responders.
Jena University Hospital, Children's Clinic, Department of Pediatric Hematology and Oncology, Jena, Germany.
Bernd
B
Gruhn
Thomas
T
Naumann
Dorothee
D
Gruner
Mario
M
Walther
Susan
S
Wittig
Sabine
S
Becker
James F
JF
Beck
Jürgen
J
Sonnemann
D000293:Adolescent; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D007223:Infant; D007527:Isoenzymes; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D011241:Prednisone / Q000494:pharmacology / Q000627:therapeutic use*; D012097:Repressor Proteins / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents; D007527:Isoenzymes; D012097:Repressor Proteins; C400300:HDAC4 protein, human; D006655:Histone Deacetylases; D011241:Prednisone
Childhood ALL; Gene expression; HDAC; Prednisone response; Vorinostat