Altered Expression of Circadian Clock Genes in Human Chronic Myeloid Leukemia

Circadian clock genes use transcriptional-translational feedback loops to control circadian rhythms. Recent studies have demonstrated that expression of some circadian clock genes displays daily oscillation in peripheral tissues including peripheral blood and bone marrow. Circadian rhythms regulate...

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Bibliographic Details
Published in:Journal of biological rhythms 2011-04, Vol.26 (2), p.136-148
Main Authors: Yang, Ming-Yu, Yang, Wen-Chi, Lin, Pai-Mei, Hsu, Jui-Feng, Hsiao, Hui-Hua, Liu, Yi-Chang, Tsai, Hui-Jen, Chang, Chao-Sung, Lin, Sheng-Fung
Format: Article
Language:English
Subjects:
Adult
Circadian Clocks - genetics
Circadian rhythm
Circadian Rhythm - genetics
Cytogenetics
Down-Regulation
Female
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Leukemic
Genes
Humans
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - blood
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism
Leukocytes
Leukocytes, Mononuclear - physiology
Male
Neutrophils - physiology
Nuclear Proteins - biosynthesis
Nuclear Proteins - genetics
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Summary:Circadian clock genes use transcriptional-translational feedback loops to control circadian rhythms. Recent studies have demonstrated that expression of some circadian clock genes displays daily oscillation in peripheral tissues including peripheral blood and bone marrow. Circadian rhythms regulate various functions of human body, and the disruption of circadian rhythm has been associated with cancer development and tumor progression. However, the direct links between aberrant circadian clock gene expression and human disorders remain largely unknown. In this study, comparisons were made between the expression profiles of 9 circadian clock genes from peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) from 18 healthy volunteers. Peripheral blood (PB) total leukocytes from 54 healthy volunteers and 95 patients with chronic myeloid leukemia (CML) were also investigated. Similar expression profiles of all 9 circadian clock genes were observed in PBMCs and PMNs of healthy individuals. In PB total leukocytes of healthy individuals, the daily pattern of PER1, PER2, PER3, CRY1, CRY2, and CKIε expression level peaked at 0800 h, and BMAL1 peaked at 2000 h. Daily pattern expression of these 7 genes was disrupted in newly diagnosed pre—imatinib mesylate—treated and blast crisis—phase patients with CML. Partial daily pattern gene expression recoveries were observed in patients with CML with complete cytogenetic response and major molecular response. The expression of CLOCK and TIM did not show a time-dependent variation among the healthy and patients with CML. These results indicate a possible association of the disrupted daily patterns of circadian clock gene expression with the pathogenesis of CML.
ISSN:0748-7304
1552-4531
DOI:10.1177/0748730410395527