PMID: 8947586Sep 1, 1996Paper

Mutation in the ligand-binding domain of the retinoic acid receptor alpha in HL-60 leukemic cells resistant to retinoic acid and with increased sensitivity to vitamin D3 analogs

Leukemia Research
B T Doré, R L Momparler

Abstract

Even though retinoic acid can induce complete remissions in patients with acute promyelocytic leukemia, the duration of response is short and further therapy with this agent is less effective, suggesting the development of drug resistance. One possible way to overcome this problem is to use retinoic acid in combination with another agent that can induce differentiation, such as vitamin D3 or its analogs. In order to understand the mechanism of drug resistance to retinoic acid, we have isolated a clone of human HL-60 myeloid leukemic cells that is resistant to all-trans retinoic acid by continuous exposure to this agent. We have observed that the resistant cell line was also resistant to 9-cis-retinoic acid and more sensitive to the antileukemic action of the vitamin D3 analog, 1,25-dihydroxy-16-ene- 23-yne-26,27-F6-cholecalciferol. In addition, this combination showed synergistic antileukemic action against the wild type HL-60 leukemic cells. DNA sequence analysis revealed a mutation in the ligand binding region of retinoic acid receptor alpha in the HL-60/RA cells in which a glycine was replaced by an aspartic acid. Using gel retardation assays, we observed a large reduction in the formation of RXR-RAR heterodimers in the HL-6...Continue Reading

References

Mar 1, 1992·Genes & Development·D J MangelsdorfR M Evans
May 26, 1991·The New England Journal of Medicine·R P WarrellA Jakubowski
Jan 1, 1990·Methods in Enzymology·A M JettenC Nervi
Apr 1, 1990·Immunological Reviews·T M Carlos, J M Harlan
May 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J Y ZhouH P Koeffler
Dec 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·A M WangD F Mark
Dec 17, 1987·Nature·V GiguereR M Evans
Sep 25, 1984·Nucleic Acids Research·P A Krieg, D A Melton
Jan 1, 1983·European Journal of Clinical Pharmacology·R K BrazzellW A Colburn
Jan 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·G AllenbyP Chambon

❮ Previous
Next ❯

Citations

Sep 12, 2002·Pharmacogenomics·Ingo K Mellinghoff, Charles L Sawyers
Dec 30, 2014·Molecular Aspects of Medicine·Alessandra di MasiClara Nervi
Jan 22, 2004·Experimental Biology and Medicine·Satei Moqattash, John D Lutton

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.