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: UMLS:C0023473 (
chronic myeloid leukemia
)
18,916
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Endocytosis is the major regulator process of tyrosine kinase receptor (RTK) functional activities.
Bridging integrator 1
(
BIN1
) is a key protein involved in RTK intracellular trafficking. Here, we report, by studying 34 patients with
chronic myeloid leukemia
(
CML
) at diagnosis, that
BIN1
gene is downregulated in
CML
as compared to healthy controls, suggesting an altered endocytosis of RTKs. Rab interactor 1 (RIN1), an activator of
BIN1
, displayed a similar behavior. Treatment of 57 patients by tyrosine kinase inhibitors caused, along with BCR-ABL1 inactivation, an increase of
BIN1
and RIN1 expression, potentially restoring endocytosis. There was a significant inverse correlation between
BIN1
-RIN1 and BCR-ABL1 expression. In vitro experiments on both
CML
and nontumorigenic cell lines treated with Imatinib confirmed these results. In order to provide another proof in favor of
BIN1
and RIN1 endocytosis function in
CML
, we demonstrated that Imatinib induced, in K562 cell line,
BIN1
-RIN1 upregulation accompanied by a parallel AXL receptor internalization into cytoplasmic compartment. This study shows a novel deregulated mechanism in
CML
patients, indicating
BIN1
and RIN1 as players in the maintenance of the abnormal RTK signaling in this hematological disease.
...
PMID:Inverse regulation of bridging integrator 1 and BCR-ABL1 in chronic myeloid leukemia. 2619 65
