Circadian rhythms are endogenous and self-sustained oscillations of multiple 
biological processes with approximately 24-h rhythmicity. Circadian genes and 
their protein products constitute the molecular components of the circadian 
oscillator that form positive/negative feedback loops and generate circadian 
rhythms. The circadian regulation extends from core clock genes to various 
clock-controlled genes that include various cell cycle genes. Aberrant 
expression of circadian clock genes, therefore, may lead to genomic instability 
and accelerated cellular proliferation potentially promoting carcinogenesis. The 
current study encompasses the investigation of simultaneous expression of four 
circadian clock genes (Bmal1, Clock, Per1 and Per2) and three clock-controlled 
cell cycle genes (Myc, Cyclin D1 and Wee1) at mRNA level and determination of 
serum melatonin levels in peripheral blood samples of 37 CLL (chronic 
lymphocytic leukemia) patients and equal number of age- and sex-matched healthy 
controls in order to indicate association between deregulated circadian clock 
and manifestation of CLL. Results showed significantly down-regulated expression 
of Bmal1, Per1, Per2 and Wee1 and significantly up-regulated expression of Myc 
and Cyclin D1 (P < 0.0001) in CLL patients as compared to healthy controls. When 
expression of these genes was compared between shift-workers and 
non-shift-workers within the CLL group, the expression was found more aberrant 
in shift-workers as compared to non-shift-workers. However, this difference was 
found statistically significant for Myc and Cyclin D1 only (P < 0.05). Serum 
melatonin levels were found significantly low (P < 0.0001) in CLL subjects as 
compared to healthy controls whereas melatonin levels were found still lower in 
shift-workers as compared to non-shift-workers within CLL group (P < 0.01). Our 
results suggest that aberrant expression of circadian clock genes can lead to 
aberrant expression of their downstream targets that are involved in cell 
proliferation and apoptosis and hence may result in manifestation of CLL. 
Moreover, shift-work and low melatonin levels may also contribute in etiology of 
CLL by further perturbing of circadian clock.