Journal of Clinical Laboratory Analysis,
Journal Year:
2022,
Volume and Issue:
36(8)
Published: June 23, 2022
Abstract
Background
Epigenetic
abnormalities
in
acute
myeloid
leukaemia
provide
us
with
a
target
for
novel
therapeutic
strategies.
The
aim
of
the
study
was
to
verify
epigenetic
regulatory
mechanism
E‐cadherin
gene
silencing
induced
by
long
non‐coding
RNA
MALAT‐1
AML.
Methods
Expression
MALAT‐1,
,
EZH2
SUZ12
and
EED
genes
AML
patients
detected
RT‐qPCR.
After
cell
lines,
levels
DNMT1
DNMT3A
DNMT3B
encoded
proteins
were
RT‐qPCR
Western
blotting.
level
CpG
island
methylation
trimethylation
modification
histone
H3K27
promoter
region
pyrosequencing
ChIP‐qPCR.
RIP‐qPCR
used
detect
interaction
between
proteins.
Results
expression
markedly
increased
down‐regulation.
A
positive
correlation
or
observed.
silencing,
up‐regulated,
whereas
down‐regulated.
blotting
consistent
those
Methylation
higher
than
that
normal
controls,
which
appeared
increase
age.
decreased
after
silencing.
suggested
might
be
enriched
SUZ12.
Conclusion
Our
findings
verified
lead
transcriptional
through
mediated
recruiting
Journal of Hematology & Oncology,
Journal Year:
2020,
Volume and Issue:
13(1)
Published: June 8, 2020
Acute
myeloid
leukemia
(AML)
is
a
common
subtype
and
has
poor
prognosis.
The
risk
of
AML
highly
related
to
age.
In
the
context
population
aging,
comprehensive
report
presenting
epidemiological
trends
evaluable
for
policy-marker
allocate
healthy
resources.This
study
was
based
on
Global
Burden
Disease
2017
database.
We
analyzed
change
incidence
rate,
death
disability-adjusted
life
year
(DALY)
rate
by
calculating
corresponding
estimated
annual
percentage
(EAPC)
values.
Besides,
we
investigated
influence
social
development
degree
AML's
potential
factors
AML-related
mortality.From
1990
2017,
gradually
increased
in
globe.
Males
elder
people
had
higher
possibility
develop
AML.
Developed
countries
tended
have
age-standardized
than
developing
regions.
Smoking,
high
body
mass
index,
occupational
exposure
benzene,
formaldehyde
were
main
mortality.
Notably,
contribution
ratio
carcinogens
significantly
low
social-demographic
index
(SDI)
region
SDI
region.Generally,
burden
became
heavier
during
past
28
years
which
might
need
more
health
resources
resolve
this
aging-associated
problem.
present
stage,
developed
with
most
incidences
deaths.
At
same
time,
middle-
or
low-middle
also
take
actions
relieve
rapidly
burden.
Cells,
Journal Year:
2023,
Volume and Issue:
12(8), P. 1163 - 1163
Published: April 14, 2023
Aging
is
an
inevitable
outcome
of
life,
characterized
by
a
progressive
decline
in
tissue
and
organ
function.
At
molecular
level,
it
marked
the
gradual
alterations
biomolecules.
Indeed,
important
changes
are
observed
on
DNA,
as
well
at
protein
that
influenced
both
genetic
environmental
parameters.
These
directly
contribute
to
development
or
progression
several
human
pathologies,
including
cancer,
diabetes,
osteoporosis,
neurodegenerative
disorders
others
aging-related
diseases.
Additionally,
they
increase
risk
mortality.
Therefore,
deciphering
hallmarks
aging
represents
possibility
for
identifying
potential
druggable
targets
attenuate
process,
then
age-related
comorbidities.
Given
link
between
aging,
genetic,
epigenetic
alterations,
given
reversible
nature
mechanisms,
precisely
understanding
these
factors
may
provide
therapeutic
approach
disease.
In
this
review,
we
center
regulatory
mechanisms
their
aging-associated
changes,
highlighting
inferences
age-associated
Journal of Medicinal Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 30, 2025
In
humans,
the
2-oxoglutarate-dependent
dioxygenases
(2-OGDDs)
catalyze
hydroxylation
reactions
involved
in
cell
metabolism,
biosynthesis
of
small
molecules,
DNA
and
RNA
demethylation,
hypoxic
response
formation
collagen.
The
reaction
is
catalyzed
by
a
highly
oxidizing
ferryl-oxo
species
produced
when
active
site
non-heme
iron
engages
molecular
oxygen.
Enzyme
activity
specifically
stimulated
l-ascorbic
acid
(ascorbate,
vitamin
C),
an
effect
not
well
mimicked
other
reducing
agents.
this
perspective
article
we
discuss
reliance
2-OGDDs
on
ascorbate
availability.
We
draw
upon
findings
from
studies
with
different
to
piece
together
comprehensive
theory
for
specific
role
supporting
enzyme
activity.
Our
discussion
centers
capacity
act
as
efficient
radical
scavenger
its
propensity
reduce
chelate
transition
metals.
addition,
consider
evidence
stereospecific
binding
site.
Cancers,
Journal Year:
2020,
Volume and Issue:
12(3), P. 637 - 637
Published: March 10, 2020
Mutations
of
the
TP53
gene
occur
in
a
subset
patients
with
acute
myeloid
leukemia
(AML)
and
confer
an
exceedingly
adverse
prognosis.
However,
whether
different
types
mutations
exert
uniformly
poor
outcome
has
not
been
investigated
yet.
Here,
we
addressed
this
issue
by
analyzing
data
1537
intensively
treated
within
protocols
German-Austrian
AML
study
group.
We
classified
depending
on
their
impact
protein
structure
according
to
evolutionary
action
(EAp53)
score
relative
fitness
(RFS).
In
98/1537
(6.4%)
patients,
108
were
detected.
While
discrimination
EAp53
did
show
survival
difference,
low-risk
high-risk
AML-specific
RFS
showed
overall
(OS;
median,
12.9
versus
5.5
months,
p
=
0.017)
event-free
(EFS;
7.3
5.2
0.054).
multivariable
analyses
adjusting
for
age,
gender,
white
blood
cell
count,
cytogenetic
risk,
type
AML,
variant
allele
frequency,
these
differences
statistically
significant
both
OS
(HR,
2.14;
95%
CI,
1.15-4.0;
EFS
1.97;
1.06-3.69;
0.033).
conclude
that
is
prognostic
value
TP53-mutated
useful
tool
therapeutic
decision-making.
OncoTargets and Therapy,
Journal Year:
2022,
Volume and Issue:
Volume 15, P. 423 - 436
Published: April 1, 2022
Abstract:
TP53
is
a
key
tumor
suppressor
gene
that
plays
an
important
role
in
regulating
apoptosis,
senescence,
and
DNA
damage
repair
response
to
cellular
stress.
Although
somewhat
rare,
-mutated
AML
has
been
identified
as
molecular
subgroup
with
prognosis
arguably
the
worst
of
any.
Survival
beyond
one
year
rare
after
induction
chemotherapy
or
without
consolidative
allogeneic
stem
cell
transplant.
rates
have
improved
hypomethylating
agents,
outcomes
remain
particularly
poor
due
short
duration.
Improvements
our
understanding
genetics
biology
led
surge
novel
treatment
options,
though
clinical
applicability
these
agents
disease
remains
largely
unknown.
This
review
will
focus
on
epidemiology,
characteristics,
significance
mutations
well
emerging
options
are
currently
being
studied.
Keywords:
acute
myeloid
leukemia,
mutation,
venetoclax,
eprenetapopt,
magrolimab
Scientific Reports,
Journal Year:
2022,
Volume and Issue:
12(1)
Published: July 20, 2022
Abstract
Aberrant
changes
in
5-hydroxymethylcytosine
(5hmC)
are
a
unique
epigenetic
feature
many
cancers
including
acute
myeloid
leukemia
(AML).
However,
genome-wide
analysis
of
5hmC
plasma
cell-free
DNA
(cfDNA)
remains
unexploited
AML
patients.
We
used
highly
sensitive
and
robust
nano-5hmC-Seal
technology
profiled
distribution
239
cfDNA
samples
from
103
patients
81
non-cancer
controls.
developed
diagnostic
model
that
precisely
differentiates
controls
with
high
sensitivity
specificity.
also
prognostic
accurately
predicts
prognosis
High
weighted
scores
(wp-scores)
were
significantly
associated
adverse
overall
survival
(OS)
both
training
(
P
=
3.31e−05)
validation
0.000464)
sets.
The
wp-score
was
genetic
risk
stratification
displayed
dynamic
varied
disease
burden.
Moreover,
we
found
wp-scores
single
gene,
BMS1
GEMIN5
predicted
OS
the
set
0.023
0.031,
respectively)
9.66e−05
0.011,
respectively).
Lastly,
our
study
demonstrated
landscape
hydroxymethylation
revealed
critical
genes
pathways
related
to
diagnosis
prognosis.
Our
data
reveal
signatures
as
accurate
markers
for
Plasma
will
be
an
effective
minimally
invasive
tool
management.
Epigenomics,
Journal Year:
2022,
Volume and Issue:
14(16), P. 965 - 986
Published: Aug. 1, 2022
Aging
as
an
inevitable
phenomenon
is
associated
with
pervasive
changes
in
physiological
functions.
There
a
relationship
between
aging
and
the
increase
of
several
chronic
diseases.
Most
age-related
disorders
are
accompanied
by
underlying
inflammatory
state,
demonstrated
local
infiltration
cells
greater
levels
proinflammatory
cytokines
bloodstream.
Within
inflammaging,
many
epigenetic
events,
especially
DNA
methylation,
change.
During
process,
due
to
aberrations
biological
processes
disrupted,
leading
emergence
or
progression
variety
human
diseases,
including
cancer,
neurodegenerative
disorders,
cardiovascular
disease
diabetes.
The
focus
this
review
on
which
involved
inflammaging-related
activities,
how
its
dysregulation
leads
disorders.Aging
natural
process
variation
One
hallmarks
changes,
directly
aging-related
methylation
one
during
aging.
Consequently,
affect
various
cellular
cause
This
discusses
role
FEBS Letters,
Journal Year:
2024,
Volume and Issue:
598(22), P. 2809 - 2828
Published: July 24, 2024
In
the
last
few
decades,
increasing
human
life
expectancy
has
led
to
inflation
of
elderly
population
and
consequently
escalation
age-related
disorders.
Biological
aging
been
associated
with
accumulation
somatic
mutations
in
Hematopoietic
Stem
Cell
(HSC)
compartment,
providing
a
fitness
advantage
HSCs
leading
clonal
hematopoiesis,
that
includes
non-malignant
malignant
conditions
(i.e.
Clonal
Hematopoiesis
Indeterminate
Potential,
Myelodysplastic
Syndrome
Acute
Myeloid
Leukemia).
The
Janus
Kinase-Signal
Transducer
Activator
Transcription
(JAK-STAT)
pathway
is
key
player
both
normal
hematopoiesis.
STATs,
particularly
STAT3
STAT5,
are
greatly
implicated
immunity,
inflammation,
leukemia,
aging.
Here,
pleiotropic
functions
JAK-STAT
age-associated
hematopoietic
defects
STAT5
inflammaging
reviewed.
Even
though
great
progress
made
deciphering
role
further
research
required
provide
deeper
understanding
molecular
mechanisms
leukemogenesis,
as
well
novel
biomarkers
therapeutic
targets
for
improved
management
