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FOXO1 repression contributes to block of plasma cell differentiation in classical Hodgkin lymphoma.
[hodgkin lymphoma, classical]
The
survival
of
classical
Hodgkin
lymphoma
(
cHL
)
cells
depends
on
activation
of
NF-κB
,
JAK
/
STAT
,
and
IRF
4
.
Whereas
these
factors
typically
induce
the
master
regulator
of
plasma
cell
(
PC
)
differentiation
PRDM
1
/
BLIMP-
1
,
levels
of
PRDM
1
remain
low
in
cHL
.
FOXO
1
,
playing
a
critical
role
in
normal
B-
cell
development
,
acts
as
a
tumor
suppressor
in
cHL
,
but
has
never
been
associated
with
induction
of
PC
differentiation
.
Here
we
show
that
FOXO
1
directly
upregulates
the
full-length
isoform
PRDM
1
α
in
cHL
cell
lines
.
We
also
observed
a
positive
correlation
between
FOXO
1
and
PRDM
1
expression
levels
in
primary
Hodgkin-
Reed
-
Sternberg
cells
.
Further
,
we
show
that
PRDM
1
α
acts
as
a
tumor
suppressor
in
cHL
at
least
partially
by
blocking
MYC
.
Here
we
provide
a
link
between
FOXO
1
repression
and
PRDM
1
α
downregulation
in
cHL
and
identify
PRDM
1
α
as
a
tumor
suppressor
in
cHL
.
The
data
support
a
potential
role
for
FOXO
transcription
factors
in
normal
PC
differentiation
.
Diseases
Validation
Diseases presenting
"positive correlation"
symptom
22q11.2 deletion syndrome
acute rheumatic fever
adrenal incidentaloma
aromatase deficiency
congenital adrenal hyperplasia
congenital diaphragmatic hernia
cutaneous mastocytosis
dedifferentiated liposarcoma
familial mediterranean fever
hodgkin lymphoma, classical
inclusion body myositis
kallmann syndrome
legionellosis
oral submucous fibrosis
trochlear dysplasia
well-differentiated liposarcoma
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