A NEW CLOCK IS RUNNING FOR MULTIPLE MYELOMA:
CIRCADIAN CLOCK PROTEIN-PERIOD 3 (PER-3)
POLYMORPHISM
Serin I.1,*, Pehlivan S.2, Demir I.3, Oyacı Y.2, Pehlivan M.3
*Corresponding Author: Istemi Serin, M.D., University of Health Sciences, Istanbul Training and
Research Hospital, Department of Hematology, Org. Nafiz GURMAN Cad., Fatih, 34098
tel.: +90 532 3172393, e-mail: serinistemi@hotmail.com
page: 37
|
|
INTRODUCTION
Multiple myeloma (MM) makes up 10% of hematological
malignancies and 1% of all cancers. It is mostly
seen in men, and the median age is reported to be about
65 years old [1]. MM, which causes excessive production
of monoclonal light chain and heavy chain, is a malign
disease of plasma cell [2]. Autologous stem cell transplantation
(ASCT) after high dose chemotherapy is the favored
standard treatment in fit patients diagnosed with MM. The
International Staging System (ISS) was made based on
levels of serum albumin and beta-2 microglobulin. Yet
in the revised ISS, in addition to the ISS, added factors
such as serum lactate dehydrogenase (LDH) and deletion
of 17p, t (4; 14), t (14; 16) are evaluated by interphase
fluorescence in situ hybridization (FISH) [1- 3].
The circadian clock (CC), which is governed via the
main center of mammalian physiology in the superior
chiasmatic nucleus, plays a role in the arrangement of
behavior of biological and physiological, as per the light
cycle and dark cycle in the daily period [4, 5]. This center
forms a link with a complex neurohumoral network via
temperature daily rhythms, photic signals by retina, social
stimuli and diet. The circadian rhythm (CR) is regulated
by CR pathway genes, the mammalian CC mechanism
has interlocking transcription-translation feedback loops,
controlled at the molecular level by a set of genes, including
NPAS2, BMAL1, CLOCK, period genes (PER-1, -2,
and -3), cryptochrome circadian regulator 1 (CRY-1 and
-2), NR1D-1 and -2. Previous studies showed that changes
of expression in these genes play a role in immune cells
and in the functions and expression of cytokines [4, 5].
The physiology of the immune system has a 24-hour CR,
and most of these cells express genes of CR. Circadian
gene expressions affect many mechanisms including cellular
and cytolytic functions and cytokine synthesis. Thus,
dysregulation or mutation of PER-3 or other clock genes
has been related with some cancers [6]. The CC Protein PER-3 (rs57875989) is situated on
chromosome 1p36.23 and has a polymorphic domain that
expresses 4 or 5 copies of the 54-bp tandem repeat sequence
(variable number tandem repeat, VNTR). This variation,
resulting from the deletion or insertion of 18 amino acids,
is linked to mood and sleep disturbances and circadian preference
in humans [6]. The PER-3 polymorphism plays an
important role in CR disorders, dysregulation of immune
system and expression of cytokines [4-8]. It has been suggested
that immune dysregulation associated with the PER-3
polymorphism contributes to chronic inflammatory processes
or diseases, and cancer biogenesis [6]. A previous study
demonstrated interaction between PER-3 polymorphism and
markers associated with chronic inflammation, including
interleukin (IL)-1, -6, interferon-gamma (IFN-Ɣ), and tumor
necrosis factor-alpha (TNF-α), and IL-6 expressions. These
were higher in patients with 4/5 or 5/5 PER-3 gene polymorphism
compared to patients with the 4/4 polymorphism [6].
It is suggested that the 4/5 or 5/5 PER-3 genotype is more
common in premenopausal breast cancer [9]. Thus, there is
increasing interest in studies investigating the relationship
between PER-3 gene polymorphisms and pre-cancerous
processes and auto-inflammatory/-immune diseases.
In this study, we intend to investigate the distributions
and clinical efficacy of the PER-3 gene polymorphism in
MM patients.
|
|
|
|
 |
Number 27
VOL. 27 (2), 2024 |
Number 27
VOL. 27 (1), 2024 |
Number 26
Number 26 VOL. 26(2), 2023 All in one |
Number 26
VOL. 26(2), 2023 |
Number 26
VOL. 26, 2023 Supplement |
Number 26
VOL. 26(1), 2023 |
Number 25
VOL. 25(2), 2022 |
Number 25
VOL. 25 (1), 2022 |
Number 24
VOL. 24(2), 2021 |
Number 24
VOL. 24(1), 2021 |
Number 23
VOL. 23(2), 2020 |
Number 22
VOL. 22(2), 2019 |
Number 22
VOL. 22(1), 2019 |
Number 22
VOL. 22, 2019 Supplement |
Number 21
VOL. 21(2), 2018 |
Number 21
VOL. 21 (1), 2018 |
Number 21
VOL. 21, 2018 Supplement |
Number 20
VOL. 20 (2), 2017 |
Number 20
VOL. 20 (1), 2017 |
Number 19
VOL. 19 (2), 2016 |
Number 19
VOL. 19 (1), 2016 |
Number 18
VOL. 18 (2), 2015 |
Number 18
VOL. 18 (1), 2015 |
Number 17
VOL. 17 (2), 2014 |
Number 17
VOL. 17 (1), 2014 |
Number 16
VOL. 16 (2), 2013 |
Number 16
VOL. 16 (1), 2013 |
Number 15
VOL. 15 (2), 2012 |
Number 15
VOL. 15, 2012 Supplement |
Number 15
Vol. 15 (1), 2012 |
Number 14
14 - Vol. 14 (2), 2011 |
Number 14
The 9th Balkan Congress of Medical Genetics |
Number 14
14 - Vol. 14 (1), 2011 |
Number 13
Vol. 13 (2), 2010 |
Number 13
Vol.13 (1), 2010 |
Number 12
Vol.12 (2), 2009 |
Number 12
Vol.12 (1), 2009 |
Number 11
Vol.11 (2),2008 |
Number 11
Vol.11 (1),2008 |
Number 10
Vol.10 (2), 2007 |
Number 10
10 (1),2007 |
Number 9
1&2, 2006 |
Number 9
3&4, 2006 |
Number 8
1&2, 2005 |
Number 8
3&4, 2004 |
Number 7
1&2, 2004 |
Number 6
3&4, 2003 |
Number 6
1&2, 2003 |
Number 5
3&4, 2002 |
Number 5
1&2, 2002 |
Number 4
Vol.3 (4), 2000 |
Number 4
Vol.2 (4), 1999 |
Number 4
Vol.1 (4), 1998 |
Number 4
3&4, 2001 |
Number 4
1&2, 2001 |
Number 3
Vol.3 (3), 2000 |
Number 3
Vol.2 (3), 1999 |
Number 3
Vol.1 (3), 1998 |
Number 2
Vol.3(2), 2000 |
Number 2
Vol.1 (2), 1998 |
Number 2
Vol.2 (2), 1999 |
Number 1
Vol.3 (1), 2000 |
Number 1
Vol.2 (1), 1999 |
Number 1
Vol.1 (1), 1998 |
|
|
