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c-JUN N-terminal kinase (JNK) is activated and contributes to tumor cell proliferation in classical Hodgkin lymphoma.
[hodgkin lymphoma, classical]
c-
JUN
N-
terminal
Kinase
(
JNK
)
is
activated
/
phosphorylated
by
upstream
MAPK
kinases
(
MKK
)
,
and
,
in
turn
,
phosphorylates
and
activates
its
major
substrate
c-
JUN
,
a
member
of
the
activator
protein-
1
(
AP
-
1
)
transcription
factors
.
c-
JUN
is
overexpressed
and
activated
in
Hodgkin
and
Reed
Sternberg
cells
(
HRS
)
of
classical
Hodgkin
lymphoma
(
cHL
)
,
however
,
the
mechanism
of
its
activation
remains
unknown
.
JNK
activation
was
immunohistochemically
assessed
in
60
cases
of
HL
and
in
a
control
group
of
151
B-
cell
non-
Hodgkin
lymphomas
.
The
biologic
effects
of
JNK
activation
in
cultured
HRS
cells
were
investigated
using
colony
formation
,
cell
growth
and
viability
assays
and
cell
cycle
analysis
by
flow
cytometry
.
Western
blotting
was
used
to
assess
protein
levels
.
p
-
JNK
was
expressed
in
90
%
of
HL
,
83
%
of
Burkitt
lymphomas
,
28
%
of
mantle
cell
lymphomas
,
23
%
of
diffuse
large
B-
cell
lymphomas
,
19
%
of
follicular
lymphomas
,
and
18
%
of
extranodal
marginal
zone
lymphomas
of
MALT
type
.
None
of
the
48
cases
of
chronic
lymphocytic
leukemia
/
small
lymphocytic
lymphoma
and
18
cases
of
plasma
cell
myeloma
showed
JNK
phosphorylation
(
P
<
001
,
Kruskall-
Wallis
test
)
.
Pharmacological
inhibition
of
JNK
activity
in
cultured
HRS
cells
resulted
in
a
significant
decrease
of
cell
growth
,
which
was
associated
with
cell
cycle
arrest
at
the
G
2
/
M
phase
.
The
cell
cycle
effects
were
linked
to
deactivation
of
c-
JUN
and
upregulation
of
its
known
target
,
the
cyclin-dependent
kinase
inhibitor
p
21
.
JNK
is
highly
activated
in
HRS
cells
,
and
may
contribute
to
uncontrolled
cell
cycle
progression
and
proliferation
of
tumor
cells
in
cHL
.
Diseases
Validation
Diseases presenting
"chronic lymphocytic leukemia"
symptom
hodgkin lymphoma, classical
monosomy 21
waldenström macroglobulinemia
well-differentiated liposarcoma
wiskott-aldrich syndrome
This symptom has already been validated