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Constitutive activation of STAT5A and STAT5B regulates IgM secretion in Waldenstrom's macroglobulinemia.
[waldenström macroglobulinemia]
Activation
of
the
Janus
kinase
family
/
signal
transducer
and
activator
of
transcription
(
JAK
/
STAT
)
signaling
pathway
has
been
associated
with
the
pathogenesis
and
progression
of
both
solid
and
hematologic
malignancies
.
We
have
detected
constitutive
activation
of
STAT
5
in
malignant
B
cells
derived
from
patients
with
Waldenström
's
macroglobulinemia
(
WM
)
.
Although
short
hairpin
RNA-mediated
knockdown
of
the
STAT
5
A
and
STAT
5
B
isoforms
did
not
affect
cellular
proliferation
,
loss
of
STAT
5
significantly
decreased
immunoglobulin
M
(
IgM
)
secretion
.
A
similar
dose-dependent
inhibition
of
IgM
secretion
was
observed
when
WM
cell
lines
were
treated
with
a
small
molecule
inhibitor
of
STAT
5
.
These
data
suggest
that
STAT
5
is
involved
in
regulating
IgM
production
in
WM
and
that
inhibition
of
STAT
5
may
represent
a
novel
therapeutic
strategy
for
lowering
IgM
levels
in
WM
patients
.
Diseases
Validation
Diseases presenting
"detected constitutive activation"
symptom
waldenström macroglobulinemia
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