International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(21), С. 11619 - 11619
Опубликована: Окт. 29, 2024
Fanconi
anemia
(FA)
represents
a
rare
hereditary
disease;
it
develops
due
to
germline
pathogenic
variants
in
any
of
the
22
currently
discovered
FANC
genes,
which
interact
with
anemia/breast
cancer-associated
(FANC/BRCA)
pathway
maintain
genome
integrity.
FA
is
characterized
by
triad
clinical
traits,
including
congenital
anomalies,
bone
marrow
failure
(BMF)
and
multiple
cancer
susceptibility.
Due
complex
genetic
background
broad
spectrum
symptoms,
diagnostic
process
requires
use
classical
cytogenetic,
molecular
cytogenetics
strictly
methods.
Recent
findings
indicate
interplay
inflammation,
oxidative
stress,
disrupted
mitochondrial
metabolism,
impaired
intracellular
signaling
pathogenesis.
Additionally,
shift
balance
towards
overproduction
proinflammatory
cytokines
prooxidant
components
associated
advanced
myelosuppression
ultimately
BMF.
Although
mechanism
BMF
very
needs
further
clarification,
appears
that
mutual
interaction
between
redox
imbalance
causes
pancytopenia.
In
this
review,
we
summarize
available
literature
regarding
phenotype,
background,
procedures
FA.
We
also
highlight
current
understanding
autophagy
process,
state,
pathways
genotoxic
stress
Abstract
Eukaryotic
cells
engage
in
autophagy,
an
internal
process
of
self-degradation
through
lysosomes.
Autophagy
can
be
classified
as
selective
or
non-selective
depending
on
the
way
it
chooses
to
degrade
substrates.
During
damaged
and/or
redundant
organelles
like
mitochondria,
peroxisomes,
ribosomes,
endoplasmic
reticulum
(ER),
lysosomes,
nuclei,
proteasomes,
and
lipid
droplets
are
selectively
recycled.
Specific
cargo
is
delivered
autophagosomes
by
specific
receptors,
isolated
engulfed.
Selective
autophagy
dysfunction
closely
linked
with
cancers,
neurodegenerative
diseases,
metabolic
disorders,
heart
failure,
etc.
Through
reviewing
latest
research,
this
review
summarized
molecular
markers
important
signaling
pathways
for
its
significant
role
cancers.
Moreover,
we
conducted
a
comprehensive
analysis
small-molecule
compounds
targeting
their
potential
application
anti-tumor
therapy,
elucidating
underlying
mechanisms
involved.
This
aims
supply
scientific
references
development
directions
biological
drug
discovery
future.
Genes,
Год журнала:
2020,
Номер
11(12), С. 1528 - 1528
Опубликована: Дек. 21, 2020
Fanconi
anemia
(FA),
a
chromosomal
instability
syndrome,
is
caused
by
inherited
pathogenic
variants
in
any
of
22
FANC
genes,
which
cooperate
the
FA/BRCA
pathway.
This
pathway
regulates
repair
DNA
interstrand
crosslinks
(ICLs)
through
homologous
recombination.
In
FA
proper
ICLs
impaired
and
accumulation
toxic
double
strand
breaks
occurs.
To
this
type
damage,
cells
activate
alternative
error-prone
pathways,
may
lead
to
formation
gross
structural
chromosome
aberrations
radial
figures
are
hallmark
FA,
their
segregation
during
cell
division
origin
subsequent
such
as
translocations,
dicentrics
acentric
fragments.
The
deficiency
has
pleiotropic
consequences
phenotype
patients
with
including
developmental
alterations,
bone
marrow
failure
an
extreme
risk
develop
cancer.
mechanisms
leading
physical
abnormalities
embryonic
development
have
not
been
clearly
elucidated,
however
features
premature
aging
chronic
inflammation
mediated
pro-inflammatory
cytokines,
results
tissue
attrition,
selection
malignant
clones
cancer
onset.
Moreover,
death
exclusive
somatic
compartment,
they
also
affect
germinal
cells,
evidenced
infertility
observed
FA.
Biomedical Reports,
Год журнала:
2021,
Номер
15(3)
Опубликована: Июль 15, 2021
Fanconi
anemia
is
a
genetic
syndrome
clinically
characterized
by
congenital
malformations
that
affect
several
human
systems,
leads
to
progressive
bone
marrow
failure
and
predisposes
an
individual
cancer,
particularly
in
the
urogenital
area
as
well
head
neck.
It
commonly
caused
biallelic
compromise
of
one
22
genes
involved
FA/BRCA
repair
pathway
most
cases.
The
diagnosis
based
on
clinical
suspicion
confirmation
using
analysis,
where
chromosomal
breakage
test
considered
gold
standard.
Other
diagnostic
methods
used
include
western
blotting,
multiplex
ligation‑dependent
probe
amplification
next‑generation
sequencing.
This
condition
has
variable
expressiveness,
which
makes
early
difficult
certain
Although
does
not
currently
allow
for
improved
cure
rates
this
condition,
it
enable
healthcare
professionals
perform
specific
systematic
follow‑up
and,
if
indicated,
transplantation
improves
mobility
mortality
affected
individuals.
present
review
article
theoretical
revision
pathophysiology,
manifestations
intended
different
specialists
general
practitioners
improve
condition.
Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Ноя. 12, 2022
Abstract
Fanconi
Anemia
(FA)
is
a
debilitating
genetic
disorder
with
wide
range
of
severe
symptoms
including
bone
marrow
failure
and
predisposition
to
cancer.
CRISPR-Cas
genome
editing
manipulates
genotypes
by
harnessing
DNA
repair
has
been
proposed
as
potential
cure
for
FA.
But
FA
caused
deficiencies
in
itself,
preventing
the
use
strategies
such
homology
directed
repair.
Recently
developed
base
(BE)
systems
do
not
rely
on
double
stranded
breaks
might
be
used
target
mutations
genes,
but
this
remains
tested.
Here
we
develop
proof
concept
therapeutic
strategy
address
two
most
prevalent
FANCA
patient
hematopoietic
stem
progenitor
cells.
We
find
that
optimizing
adenine
editor
construct,
vector
type,
guide
RNA
format,
delivery
conditions
leads
very
effective
modification
multiple
backgrounds.
Optimized
restored
expression,
molecular
function
pathway,
phenotypic
resistance
crosslinking
agents.
ABE8e
mediated
primary
cells
from
patients
was
both
genotypically
pathway
function,
indicating
future
clinical
application
Pediatric Blood & Cancer,
Год журнала:
2021,
Номер
68(4)
Опубликована: Янв. 23, 2021
Interferon-gamma
(IFN-γ)
plays
a
key
role
in
the
pathophysiology
of
hemophagocytic
lymphohistiocytosis
(HLH),
and
available
evidence
also
points
to
other
conditions,
including
aplastic
anemia
(AA)
graft
failure
following
allogeneic
hematopoietic
stem
cell
transplantation.
Recently,
therapeutic
potential
IFN-γ
inhibition
has
been
documented;
emapalumab,
an
anti-IFN-γ
monoclonal
antibody,
approved
United
States
for
treatment
primary
HLH
that
is
refractory,
recurrent
or
progressive,
patients
with
intolerance
conventional
therapy.
Moreover,
ruxolitinib,
inhibitor
JAK/STAT
intracellular
signaling,
currently
being
investigated
treating
HLH.
In
AA,
inhibits
hematopoiesis
by
disrupting
interaction
between
thrombopoietin
its
receptor,
c-MPL.
Eltrombopag,
small-molecule
agonist
c-MPL,
acts
at
different
binding
site
thus
able
circumvent
inhibitory
effects.
Ongoing
trials
will
elucidate
neutralization
secondary
future
studies
could
explore
this
strategy
controlling
hyperinflammation
due
CAR
T
cells.
International Journal of Molecular Sciences,
Год журнала:
2021,
Номер
22(12), С. 6275 - 6275
Опубликована: Июнь 10, 2021
Hereditary
anemia
has
various
manifestations,
such
as
sickle
cell
disease
(SCD),
Fanconi
anemia,
glucose-6-phosphate
dehydrogenase
deficiency
(G6PDD),
and
thalassemia.
The
available
management
strategies
for
these
disorders
are
still
unsatisfactory
do
not
eliminate
the
main
causes.
As
genetic
aberrations
causes
of
all
forms
hereditary
optimal
approach
involves
repairing
defective
gene,
possibly
through
transplantation
normal
hematopoietic
stem
cells
(HSCs)
from
a
matching
donor
or
gene
therapy
approaches
(either
in
vivo
ex
vivo)
to
correct
patient's
HSCs.
To
clearly
illustrate
importance
this
paper
provides
review
aberration,
epidemiology,
clinical
features,
current
management,
endeavors
related
SCD,
thalassemia,
G6PDD.
Moreover,
we
expound
future
research
direction
HSC
derivation
induced
pluripotent
(iPSCs),
edit
HSCs,
risk
mitigation,
their
perspectives.
In
conclusion,
gene-corrected
promising
outcomes
it
may
overcome
limitation
source
allogenic
bone
marrow
transplantation.
Cancers,
Год журнала:
2020,
Номер
12(10), С. 3006 - 3006
Опубликована: Окт. 16, 2020
The
mismatch
repair
(MMR)
system
has
a
major
role
in
the
detection
and
correction
of
DNA
replication
errors,
resulting
from
polymerase
slippage
or
nucleotides
misincorporation.
Specific
inherited/acquired
alterations
epigenetic
inactivation
MMR
genes
are
associated
with
microsatellite
instability
(MSI):
loss
crucial
function
repairing
can
promote
carcinogenesis
by
favoring
accumulation
thousands
mutations
broad
spectrum
different
anatomic
sites
such
as
colon,
stomach,
prostate,
esophagus,
endometrium,
lung
head
neck.
Recent
extensive
data
suggest
that
tumor
mutational
burden
strongly
correlates
clinical
response
to
immunotherapy
using
checkpoint
inhibitors
this
is
influenced
deficiency
wide
range
human
solid
cancers.
In
context,
few
about
point
available
for
neck
cancer
(HNC).
review,
we
discuss
MSI
HNC
pathogenesis.
Furthermore,
summarizing
on
how
they
influence
progression
precancerous
lesions
risk
recurrence
second
primary
tumors,
want
define
current
management
HNC.
Finally,
analyze
complex
interaction
between
cells
immune
addressing
now
potential
correlation
