Arteriosclerosis Thrombosis and Vascular Biology,
Год журнала:
2024,
Номер
44(3), С. 690 - 697
Опубликована: Янв. 25, 2024
BACKGROUND:
Clonal
hematopoiesis
of
indeterminate
potential
(CHIP)
is
an
acquired
genetic
risk
factor
for
both
leukemia
and
cardiovascular
disease.
It
results
in
proinflammatory
myeloid
cells
the
bone
marrow
blood;
however,
how
these
behave
tissue
remains
unclear.
Our
study
aimed
at
investigating
whether
CHIP-mutated
macrophages
accumulate
preferentially
tissues
examining
transcriptome
from
DNMT3A
(DNA
methyltransferase
3
alpha)
or
TET2
(Tet
methylcytosine
dioxygenase
2)
mutation
carriers.
METHODS:
We
recruited
patients
undergoing
carotid
endarterectomy
heart
surgeries
to
screen
CHIP
carriers
using
targeted
genomic
sequencing.
Myeloid
lymphoid
were
isolated
blood
collected
during
flow
cytometry.
DNA
RNA
extracted
sorted
subjected
variant
allele
frequency
measurement
droplet
digital
polymerase
chain
reaction
transcriptomic
profiling
bulk
sequencing,
respectively.
RESULTS:
Using
reaction,
we
detected
similar
monocytes
atheromas
tissues,
even
among
with
without
CCR2
(C-C
motif
chemokine
receptor
expression.
Bulk
sequencing
revealed
a
gene
profile
compared
those
noncarriers.
CONCLUSIONS:
Quantitatively,
did
not
but
qualitatively,
they
expressed
more
disease-prone
phenotype.
Cancer Discovery,
Год журнала:
2024,
Номер
14(3), С. 396 - 405
Опубликована: Март 1, 2024
Summary:
The
recognition
of
host
genetic
factors
underlying
susceptibility
to
hematopoietic
malignancies
has
increased
greatly
over
the
last
decade.
Historically,
germline
predisposition
was
thought
primarily
affect
young.
However,
emerging
data
indicate
that
develop
in
people
all
ages
across
human
lifespan
can
derive
from
predisposing
conditions
and
are
not
exclusively
observed
younger
individuals.
age
at
which
manifest
appears
correlate
with
distinct
biological
pathways.
Progression
having
a
deleterious
variant
being
diagnosed
overt
malignancy
involves
complex,
multistep
gene–environment
interactions
key
external
triggers,
such
as
infection
inflammatory
stimuli,
driving
clonal
progression.
Understanding
mechanisms
by
predisposed
clones
transform
under
specific
pressures
may
reveal
strategies
better
treat
even
prevent
occurring.
Recent
unbiased
genome-wide
sequencing
studies
children
adults
have
revealed
novel
genes
disease-causing
variants
origin.
This
paradigm
shift
is
spearheaded
findings
myelodysplastic
syndrome/acute
myeloid
leukemia
(MDS/AML)
well
acute
lymphoblastic
leukemia,
but
it
also
encompasses
other
cancer
types.
Although
without
challenges,
field
advancing
quickly,
understanding
basis
risk
affects
therapeutic
decisions
counseling
testing
at-risk
family
members.
Annual Review of Genomics and Human Genetics,
Год журнала:
2024,
Номер
25(1), С. 329 - 351
Опубликована: Авг. 27, 2024
Clonal
hematopoiesis
(CH)
is
an
age-related
process
whereby
hematopoietic
stem
and
progenitor
cells
(HSPCs)
acquire
mutations
that
lead
to
a
proliferative
advantage
clonal
expansion.
The
most
commonly
mutated
genes
are
epigenetic
regulators,
DNA
damage
response
genes,
splicing
factors,
which
essential
maintain
functional
HSPCs
frequently
involved
in
the
development
of
hematologic
malignancies.
Established
risk
factors
for
CH,
including
age,
prior
cytotoxic
therapy,
smoking,
increase
acquiring
CH
and/or
may
fitness.
has
emerged
as
novel
factor
many
diseases,
such
malignancies,
cardiovascular
disease,
diabetes,
autoimmune
disorders,
among
others.
Future
characterization
mechanisms
driving
evolution
will
be
critical
develop
preventative
therapeutic
approaches.
Studies
suggest
that
clonal
hematopoiesis
of
indeterminate
potential
(CHIP)
may
increase
risk
hematologic
malignancy
and
cardiovascular
disease,
including
stroke.
However,
few
studies
have
investigated
plausible
environmental
factors
for
CHIP
such
as
radon,
despite
the
climate-related
increases
in
documented
infrequency
testing
this
common
indoor
air
pollutant.The
purpose
study
was
to
estimate
related
an
established
mutagen.
Cancer Discovery,
Год журнала:
2024,
Номер
14(9), С. 1717 - 1731
Опубликована: Май 9, 2024
Abstract
Clonal
hematopoiesis
(CH)
is
a
phenomenon
of
clonal
expansion
hematopoietic
stem
cells
driven
by
somatic
mutations
affecting
certain
genes.
Recently,
CH
has
been
linked
to
the
development
hematologic
malignancies,
cardiovascular
diseases,
and
other
conditions.
Although
most
frequently
mutated
driver
genes
have
identified,
systematic
landscape
capable
initiating
this
still
lacking.
In
study,
we
trained
machine
learning
models
for
12
recurrent
identify
their
mutations.
These
outperform
expert-curated
rules
based
on
prior
knowledge
function
these
Moreover,
application
across
almost
half
million
donors
UK
Biobank
reproduces
known
associations
between
age,
prevalence
several
diseases
We
thus
propose
that
support
accurate
identification
healthy
individuals.
Significance:
developed
validated
gene-specific
mutations,
showing
advantage
with
respect
rules.
can
clinical
interpretation
in
newly
sequenced
See
related
commentary
Arends
Jaiswal,
p.
1581
Abstract
Recent
observational
studies
have
found
an
association
between
Clonal
Hematopoesis
(CH)
and
strokes
but
with
incomplete
results.
This
study
aims
to
comprehensively
characterize
mutation‐specific
effects
of
CH
on
ischemic
hemorrhagic
stroke
subtypes
90‐day
functional
outcomes
through
publicly
available
genome‐wide
(GWAS)
cohorts
Mendelian
Randomization.
TET2
is
associated
increased
risk
overall
(OR
=
1.06,
P
0.02),
1.05,
0.03),
transient
attack
1.07,
0.01)
small
vessel
1.29,
0.01),
as
well
adverse
modified
Rankin
scale
(mRS
≥
3)
before
1.34,
0.005)
after
adjusted
for
age,
sex,
severity
1.30,
0.02).
While
the
presence
any
mutation
intracerebral
hemorrhage
(ICH)
1.21,
specific
mutations,
SRSF2
ASXL1
are
protective
against
ICH
0.9,
0.04)
nontraumatic
subarachnoid
0.92,
respectively.
In
conclusion,
provided
genetic
evidence
that
strongly
poor
recovery.
Future
clarifying
relationship
needed.
