Less than a third of adults patients with acute myeloid leukemia (AML) are cured by current treatments, emphasizing the need for new approaches to therapy. We previously demonstrated that besides playing a role in drug-resistant leukemia cell lines, multidrug resistance protein 4 (MRP4/ABCC4) regulates leukemia cell proliferation and differentiation through the endogenous MRP4/ABCC4 substrate, cAMP. Here, we studied the role of MRP4/ABCC4 in tumor progression in a mouse xenograft model and in leukemic stem cells (LSCs) differentiation. We found a decrease in the mitotic index and an increase in the apoptotic index associated with the inhibition of tumor growth when mice were treated with rolipram (PDE4 inhibitor) and/or probenecid (MRPs inhibitor). Genetic silencing and pharmacologic inhibition of MRP4 reduced tumor growth. Furthermore, MRP4 knockdown induced cell cycle arrest and apoptosis in vivo. Interestingly, when LSC population was isolated, we observed that increased cAMP levels and MRP4/ABCC4 blockade resulted in LSCs differentiation. Taken together, our findings show that MRP4/ABCC4 has a relevant role in tumor growth and apoptosis and in the eradication of LSCs, providing the basis for a novel promising target in AML therapy.
Pharmacology, Toxicology and Pharmaceutical Science
5
10%
Chemistry
3
6%
Other
3
6%
Unknown
9
18%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 November 2016.
All research outputs
#18,480,433
of 22,899,952 outputs
Outputs from Oncotarget
#8,449
of 14,331 outputs
Outputs of similar age
#169,278
of 237,582 outputs
Outputs of similar age from Oncotarget
#92
of 158 outputs
Altmetric has tracked 22,899,952 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 14,331 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.5. This one is in the 26th percentile – i.e., 26% of its peers scored the same or lower than it.
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We're also able to compare this research output to 158 others from the same source and published within six weeks on either side of this one. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.
