We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
LGC Clinical Diagnostics

Download Mobile App




Success of Anti-Leukemia Compound Expected to Boost Drug Development Efforts

By LabMedica International staff writers
Posted on 18 Jul 2016
Print article
Image: An artist’s concept of how a candidate drug fits precisely in BRD9\'s deep bromodomain binding pocket. In preclinical tests, the drug\'s binding prevented AML cells from proliferating (Photo courtesy of Vakoc Lab, Cold Spring Harbor Laboratory).
Image: An artist’s concept of how a candidate drug fits precisely in BRD9\'s deep bromodomain binding pocket. In preclinical tests, the drug\'s binding prevented AML cells from proliferating (Photo courtesy of Vakoc Lab, Cold Spring Harbor Laboratory).
Cancer researchers have identified the active site of a protein required for growth and spread of the blood cancer acute myeloid leukemia (AML), and have designed a drug that blocks the site and suppresses the proliferation of mouse and human AML cell lines in vitro.

AML is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. The symptoms of AML are caused by replacement of normal bone marrow with leukemic cells, which causes a drop in red blood cells, platelets, and normal white blood cells. Symptoms include fatigue, shortness of breath, easy bruising and bleeding, and increased risk of infection. AML progresses rapidly and is typically fatal within weeks or months if left untreated.

Investigators at Cold Spring Harbor Laboratory (NY, USA) and their colleagues at the biopharmaceutical company Boehringer Ingelheim (Ingelheim, Germany) reported in the July 4, 2016, online edition of the journal Nature Chemical Biology that AML cells required the BRD9 (Bromodomain-containing protein 9) subunit of the SWI−SNF chromatin-remodeling complex to sustain transcription of the MYC oncogene and the rapid cell proliferation that it caused.

The investigators derived small-molecule inhibitors of the BRD9 bromodomain that selectively suppressed the proliferation of mouse and human AML cell lines. To establish these effects as on-target, they engineered a bromodomain-swap allele of BRD9 that retained functionality despite a radically altered bromodomain pocket. Expression of this allele in AML cells conferred resistance to the antiproliferative effects of the compound series, thus establishing BRD9 as the relevant cellular target.

"We were of course pleased with these results," said senior author Dr. Christopher Vakoc, an associate professor at Cold Spring Harbor Laboratory. "But we set an even higher bar. We wanted to be able to show, unambiguously, how the drug worked - we wanted to prove that its target in AML cells was the bromodomain of the BRD9 protein. As the age of precision medicine begins, this is an important issue, a matter of sink or swim for some candidate drugs. Here we have described a simple new approach that can unambiguously assign the therapeutic effect of a drug to a single binding site."

Related Links:
Cold Spring Harbor Laboratory
Boehringer Ingelheim
Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
One Step HbA1c Measuring System
GREENCARE A1c
Anti-Cyclic Citrullinated Peptide Test
GPP-100 Anti-CCP Kit
Gold Member
Reagent Reservoirs
Reagent Reservoirs

Print article

Channels

Clinical Chemistry

view channel
Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)

POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection

Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more

Molecular Diagnostics

view channel
Image: The study showed the blood-based cancer screening test detects 83% of people with colorectal cancer with specificity of 90% (Photo courtesy of Guardant Health)

Blood Test Shows 83% Accuracy for Detecting Colorectal Cancer

Colorectal cancer is the second biggest cause of cancer deaths among adults in the U.S., with forecasts suggesting 53,010 people might die from it in 2024. While fewer older adults are dying from this... Read more

Hematology

view channel
Image: The Gazelle Hb Variant Test (Photo courtesy of Hemex Health)

First Affordable and Rapid Test for Beta Thalassemia Demonstrates 99% Diagnostic Accuracy

Hemoglobin disorders rank as some of the most prevalent monogenic diseases globally. Among various hemoglobin disorders, beta thalassemia, a hereditary blood disorder, affects about 1.5% of the world's... Read more

Microbiology

view channel
Image: The new platform is designed to perform blood-based diagnoses of nontuberculosis mycobacteria (Photo courtesy of 123RF)

New Blood Test Cuts Diagnosis Time for Nontuberculous Mycobacteria Infections from Months to Hours

Breathing in nontuberculous mycobacteria (NTM) is a common experience for many people. These bacteria are present in water systems, soil, and dust all over the world and usually don't cause any problems.... Read more

Industry

view channel
Image: These new assays are being developed for use on the recently introduced DxI 9000 Immunoassay Analyzer (Photo courtesy of Beckman Coulter)

Beckman Coulter and Fujirebio Expand Partnership on Neurodegenerative Disease Diagnostics

Beckman Coulter Diagnostics (Brea, CA, USA) and Fujirebio Diagnostics (Tokyo, Japan) have expanded their partnership focused on the development, manufacturing and clinical adoption of neurodegenerative... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.