Downregulation of JUNB mRNA expression in advanced phase chronic myelogenous leukemia.
JUNB inactivation in transgenic mice results in a myeloproliferative disorder that closely resembles human chronic myelogenous leukemia (CML). It has been reported that downregulation of JUNB expression is a universal phenomenon in patients with CML due aberrant DNA methylation of its promoter. Based on this, we studied methylation and gene expression levels of JUNB in CML. We analyzed the methylation status of the JUNB gene in 6 cell lines and in 102 patients with CML using several bisulfite PCR assays. JUNB expression was analyzed using real-time PCR and gene expression profiling. JUNB methylation was not observed in any of the cell lines studied, and only in 3% of patients with CML. Despite the lack of JUNB methylation, JUNB was expressed at low levels both in CML cell lines (median dCT -6.86; range -5.87 to -9.61), and in patients with CML in blastic phase (BP) (median dCT -3.95; range -1.48 to -6.29) (p = 0.002). Finally, we evaluated JUNB expression in 82 additional patients with CML by gene expression arrays. We found that JUNB was significantly downregulated in advanced phase CML in contrast to chronic phase CML (median log ratio difference in expression = 0.53). Overall, our results indicate that JUNB expression is downregulated in advanced phase CML through a mechanism independent from DNA methylation.
Hoshino
Koyu
K
Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77230-1402, USA.
Quintás-Cardama
Alfonso
A
Radich
Jerald
J
Dai
Hongyui
H
Yang
Hui
H
Garcia-Manero
Guillermo
G
D000818:Animals; D045744:Cell Line, Tumor; D019175:DNA Methylation; D017931:DNA Primers; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics; D015183:Restriction Mapping; D014158:Transcription, Genetic
D017931:DNA Primers; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D012334:RNA, Neoplasm