Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: UMLS:C0023473 (
chronic myeloid leukemia
)
18,916
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Imatinib metylase is the first choice treatment for BCR/ABL positive
chronic myelogenous leukemia
(
CML
). However, as some
CML
patients develop resistance to imatinib therapy, there is a significant interest in development of alternative treatment strategies, such as identifying targets other than BCR/ABL that may participate in
CML
. Previously, we demonstrated strong PCNA up-regulation in
CML
patients. To further study its role in
CML
pathogenesis, we performed silencing of PCNA expression followed by array experiments. PCNA inhibition led to down-regulation of CDK1, CDK4, PLK1, ERK3, JNK1, STAT5, and several inhibitors of apoptosis (DAXX, Mdm2, survivin). The following genes were up-regulated: CDK inhibitors p21 and
p19-INK4D
, pro-apoptotic FAST kinase, fibronectin, etc. However, as PCNA affects cell growth in naturally proliferating cells as well as in cancerous cells, it seems to act a secondary role relating to proliferation activity of leukemic cells.
...
PMID:Expression analysis of PCNA gene in chronic myelogenous leukemia--combined application of siRNA silencing and expression arrays. 1707 Sep 5
Chronic myeloid leukemia
(
CML
) is a kind of myeloproliferative disorder caused by a constitutively active BCR-ABL tyrosine kinase. Tyrosine kinase inhibitors (TKIs), imatinib and its derivatives, have achieved great progress in the treatment of
CML
. However, many
CML
patients do not respond to TKIs alone. p19
INK4d
, a cyclin-dependent kinase inhibitor, plays important roles in proliferation, DNA damage repair, apoptosis and cell differentiation, but its role in
CML
is unknown. Herein, we found that the expression of p19
INK4d
in
CML
patients was significantly lower than that in healthy controls. p19
INK4d
overexpression inhibits cell proliferation through cell cycle arrest, and cooperates with imatinib to inhibit
CML
more effectively in vitro and in vivo. Mechanistically, p19
INK4d
decreased the expression of BCR-ABL and its downstream molecules p-Mek1/2, moreover, the expression of Gli-1, c-myc, MUC1, Shh and TC48 also reduced significantly. Collectively, p19
INK4d
inhibits proliferation and enhances imatinib efficacy in the treatment of
CML
. These findings maybe have implications for developing potential targets to increase imatinib sensitivity for
CML
.
...
PMID:p19
INK4d
inhibits proliferation and enhances imatinib efficacy through BCR-ABL signaling pathway in chronic myeloid leukemia. 3271 Dec 19
