CRISPR Technique Shows New Protein Enzymatic Function in Acute Myeloid Leukemia

In a paper published in Nature Chemical Biology, Harvard University assistant professor of Chemistry and Chemical Biology, Brian Liau, used a new gene-editing technique to expose more intimate details of why certain acute myeloid leukemia (AML) drugs sometimes fail in certain individuals and disproved previous assumptions regarding how they work.
Investigators focused on a specific sub-type of AML, which has mutated genes that cause a shift in a blood cell’s epigenetic state, leading to uncontrollable growth. According to the press release, new drugs target the enzymes that control the conversation between cells in order to ultimately reverse this malfunction. It has been determined that the enzyme target for AML is called lysine-specific histone demethylase 1 (LSD1), however, LSD1-targeting drugs rarely work, according to the study.
Investigators studied the “essential” portions of the enzyme in order to halt the protein, and therefore the disease, from uncontrollable growth. In order to do this, they used CRISPR-scanning, a gene-editing tool capable of making precise cuts in the genetic code (DNA).
The investigators used CRISPR to execute systematic but random slices in many AML-relevant genes at once. Afterwards, they were able to classify the weaknesses within the LSD1 so that the drugs can more easily target them.
In order to avoid strengthening the mutations, Lau and his colleagues examined how a drug interacts with each mutant, a technique called CRISPR-suppressor scanning. It is their belief that developers can use the information about the proliferation or suppression of malignant growth to subvert the protein’s new defenses.
Regarding the CRISPR-suppressor scanning, Lau said that tweaking the drug can create “bumps” or “holes” in the protein.
“If the bump-hole complement each other, we can tease this information apart with the methodology,” he said.
The study found that drugs targeting LSD1 shut down the protein's enzymatic function, but this function is not as critical to cancer growth as previously assumed. It also showed that the drugs can cut off communication between LSD1 and a transcription factor (GFI1B).
According to the press release, although the drugs worked because they disrupted both actions some of the time, Lau and his colleagues’ technique demonstrated that LSD1-GFI1B relationship is the most critical for AML survival. It could also explain why certain AML subtypes rely so heavily on LSD1.
The investigators hope that armed with this new information, drug developers can focus their work, hasten drug development, and produce a more targeted treatment, according to the release.

Stay up to date on the latest news in specialty pharmacy by getting Specialty Pharmacy Times in your mailbox or inbox for free!

Click here to sign up for free for the bi-monthly Specialty Pharmacy Times print journal delivered to your address.

Click here to sign up for our email newsletters delivered every Monday, Wednesday, and Friday, in addition to breaking news alerts.

Click here to follow us on Facebook. 

Click here to follow us on Twitter. 

Click here to join our LinkedIn group. 

Related Articles

Study recommends similar clinical thresholds for diagnosing and managing giant cell arteritis for patients of different ethnicities.
The approval of fedratinib (Inrebic, Celgene) provides another treatment option for patients with myelofibrosis, a rare bone marrow disorder.
Top news of the week from Specialty Pharmacy Times.
Company Profile >
Industry Guide >
Market News >
Peer Exchange >
Conferences >
Subscribe >
Specialty Times Resources
About Us
Contact Us
Terms & Conditions
MJH Associates >
Pharmacy Times
American Journal of Managed Care
MD Magazine
Targeted Oncology
Physicians' Education Resource
Pharmacy & Healthcare Communications, LLC
2 Clarke Drive
Suite 100
Cranbury, NJ 08512
P: 609-716-7777
F: 609-716-4747

Copyright Specialty Pharmacy Times 2006-2019
Pharmacy & Healthcare Communications, LLC. All Rights Reserved.