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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-05-1598.
Submitted May 30, 2002
Accepted December 10, 2002
JunB gene expression is inactivated by methylation in chronic myeloid leukemia
Ming-Yu Yang, Ta-Chih Liu, Jan-Gowth Chang, Pai-Mei Lin, and Sheng-Fung Lin*
Department of Hematology-Oncology, Kaoshiung Medical University Hospital, Kaohsiung, Taiwan
Department of Molecular Medicine, China Medical College Hospital, Taichung, Taiwan
Department of Nursing, I-Shou University, Kaohsiung, Taiwan
* Corresponding author; email: shlin{at}cc.kmu.edu.tw.
JunB is a component of the Jun family genes of the activating protein-1 transcription factors that are important in the control of cell growth, differentiation and neoplastic transformation. Recently, it was demonstrated that transgenic mice specifically lacking JunB expression in the myeloid lineage developed a transplantable myeloproliferative disease, eventually progressing to blast crisis that resembled human chronic myeloid leukemia.(CML). To gain further insights into the role of JunB in human CML, we examined peripheral blood from normal individuals (17 cases) and CML patients (11 in blastic crisis and 21 in chronic phase) by real-time quantitative reverse transcription-polymerase chain reaction analysis for the expression of JunB. The results showed the expression levels of JunB were significantly impaired in CML cases (blastic crisis < chronic phase < normal). Mutational analysis of the whole gene and methylation analysis of CpGs sites at the promoter area were further performed to investigate the possible mechanisms. However, no mutation was found within the coding region or the 9 flanking evolutionarily conserved regions in all CML cases. Interestingly, in the promoter area of JunB gene, most of the CpG sites were methylated in CML cases; in contrast, none of these CpG sites were methylated in normal cases. Demethylation by treatment of hypermethylated K562 cells with 5'-aza-2'-deoxycytidine resulted in partial reactivation of JunB expression. Our results suggest that the downregulated JunB expression in CML was due to the inactivation of JunB gene by methylation and the differential expression was correlated to the ratio of cells being methylated.
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