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)
Polyamines are critical elements in mammals, but it remains unknown whether adenosyl methionine decarboxylase (
AMD1
), a rate-limiting enzyme in polyamine synthesis, is required for myeloid leukemia. Here, we found that leukemic stem cells (LSCs) were highly differentiated, and leukemia progression was severely impaired in the absence of
AMD1
in vivo.
AMD1
was highly upregulated as
chronic myeloid leukemia
(
CML
) progressed from the chronic phase to the blast crisis phase, and was associated with the poor prognosis of
CML
patients. In addition, the pharmacological inhibition of
AMD1
by AO476 treatment resulted in a robust reduction of the progression of leukemic cells both in vitro and in vivo. Mechanistically,
AMD1
depletion induced loss of mitochondrial membrane potential and accumulation of reactive oxygen species (ROS), resulting in the differentiation of LSCs via oxidative stress and aberrant activation of unfolded protein response (UPR) pathway, which was partially rescued by the addition of polyamine. These results indicate that
AMD1
is an essential element in the progression of myeloid leukemia and could be an attractive target for the treatment of the disease.
...
PMID:AMD1 is required for the maintenance of leukemic stem cells and promotes chronic myeloid leukemic growth. 3320 90
