Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.10.2 (
focal adhesion kinase
)
44,029
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Despite the identification of several oncogenic driver mutations leading to constitutive JAK-STAT activation, the cellular and molecular biology of myeloproliferative neoplasms (MPN) remains incompletely understood. Recent discoveries have identified underlying disease-modifying molecular aberrations contributing to disease initiation and progression. Here, we report that deletion of
Nol3
(
Nucleolar protein 3
) in mice leads to an MPN resembling primary myelofibrosis (PMF).
Nol3
-/-
MPN mice harbor an expanded Thy1
+
LSK
stem cell population exhibiting increased cell cycling and a myelomonocytic differentiation bias. Molecularly, this phenotype is mediated by
Nol3
-/-
-induced JAK-STAT activation and downstream activation of
cyclin-dependent kinase 6
(
Cdk6
) and
Myc
Nol3
-/-
MPN Thy1
+
LSK
cells share significant molecular similarities with primary CD34
+
cells from PMF patients.
NOL3
levels are decreased in CD34
+
cells from PMF patients, and the
NOL3
locus is deleted in a subset of patients with myeloid malignancies. Our results reveal a novel genetic PMF-like mouse model and identify a tumor suppressor role for
NOL3
in the pathogenesis of myeloid malignancies.
...
PMID:A myeloid tumor suppressor role for
NOL3
. 2823 69
