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:C0023418 (
leukemia
)
93,477
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Most patients with acute myeloid leukemia (AML) achieve complete remission (CR) after induction chemotherapy, however, in some patients, the disease subsequently relapses and may lead to death.
Leukemia
stem cells (LSC) have been identified as the main cause for recurrence. Increased
aldehyde dehydrogenase
(ALDH
high
) activity in a variety of cancer stem cells prevents effective action of chemotherapeutic drugs. In this study, we found that approximately 50.7% of AML patients had ALDH
high
, and the presence of ALDH
high
stem cells was associated with poor cytogenetic prognosis. Lentiviral vector transduced ALDH
high
leukemia
cell lines are insensitive to the conventional chemotherapy drug cytarabine, and inhibition of ALDH activity by disulfiram (DSF) can increase the sensitivity of ALDH
high
leukemia
cells to cytarabine. Unlike traditional chemotherapy drugs, DSF is not toxic to healthy umbilical cord blood stem cells. An ALDH
high
leukemia
cell xenograft model was established using immunodeficient mice to mimic the disease environment, and DSF and cytarabine were found to eliminate the ALDH
high
leukemia
cells in transplanted mice while not affecting the healthy blood cells of mice. These findings suggest that DSF may have therapeutic potential by inhibiting ALDH activity and thereby increasing chemosensitivity.
...
PMID:Disulfiram/cytarabine eradicates a subset of acute myeloid leukemia stem cells with high aldehyde dehydrogenase expression. 3222 55
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