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:3.5.1.1 (
asparaginase
)
2,695
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Acquired drug resistance in childhood T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. In this study, a novel gene therapy target for childhood T-ALL to overcome chemoresistance was discovered:
TFDP3
increased in the minimal residual disease (MRD) positive childhood T-ALL patients. Then, we established a preclinical model of resistance to induction therapy to examine the functional relevance of
TFDP3
to chemoresistance in MRD derived from Jurkat/E6-1. Jurkat xenografts in NOD/SCID mice were exposed to a four drug combination (VXLD) of vincristine (VCR), dexamethasone (DEX),
L-asparaginase
(L-asp) and daunorubicin (DNR). During the 4-week VXLD treatment, the level of
TFDP3
increased 4-fold. High expression of
TFDP3
was identified in the re-emerging lines (Jurkat/MRD) with increased chemoresistance, which is correlated with partially promoter demethylation of
TFDP3
. Downregulation of
TFDP3
by RNA interference reversed chemoresistance in Jurkat/MRD accompanied by reinstated E2F1 activity that coincided with increased levels of p53, p73, and associated proapoptotic target genes. Importantly,
TFDP3
silencing in vivo induced apparent benefit to overcome chemoresistance in combination with VXLD treatment. Collectively,
TFDP3
confers chemoresistance in MRD within childhood T-ALL, indicating that
TFDP3
is a potential gene therapy target for residual cancer.
...
PMID:TFDP3 confers chemoresistance in minimal residual disease within childhood T-cell acute lymphoblastic leukemia. 2790 57
