GENE ONLINE|News &
Opinion
Blog

2020-04-23| R&DTechnology

CRISPR Helps Unearth Novel drug Target for Leukemia

by Sahana Shankar
Share To

By Sahana Shankar, Ph.D. candidate

Scientists from UCSD identify key regulators of aggressive, chronic myeloid leukemia via a genome-wide CRISPR screen.

Leukemias are one of the most aggressive cancers which affect both adults and children with poor prognosis and survival rates. In a new study, published in Nature Cancer, investigators from the University of California, San Diego School of Medicine report a new strategy to combat it. They employ the CRISPR-Cas9 technology to identify novel regulators of blood cancers, specifically chronic myeloid leukemia (CML) that is difficult to treat in advanced stages.

Since its arrival, CRISPR has facilitated DNA manipulation with unprecedented precision and accuracy, a capability that has been regarded as the holy grail of medicine and biological research for long. This study once again demonstrates that CRISPR is an effective tool to perform in vivo genetic screens.

RNA-binding proteins (RBPs) are essential to maintaining cells as they sustain cell proliferation, post-transcriptional regulation, and other aspects of cell behavior. They bind to specific RNA sequences to drive mRNA translation, stability, transport, and localization. Many RBPs are known to be misregulated in cancers and contribute to tumor development.

Using primary cancer cells, the authors blocked a wide spectrum of genes using CRISPR-Cas9 to identify potential therapeutic targets that promote cancer growth. According to lead author, Dr. Tannishtha Reya, “the study also shows, for the first time, that whole genome CRISPR-based screens can, in fact, be carried out in a manner that is much more physiologically relevant: using primary cancer cells and in the setting of the native microenvironment.” From the genome-wide study, the team discovered 6 RBPs to be abundantly expressed in leukemia stem cells and critical regulators of myeloid leukemia.

They performed a proof-of-study by characterizing the double stranded RBP Staufen 2 (Stau2) as a driver of leukemia stem cell proliferation and drug resistance. Stau2 was previously a known regulator of the brain and nervous system development. To validate their findings, the team developed a Stau2 knockout mouse model to understand its role in cancer regulation and demonstrated a significant decrease in leukemia cell growth, proliferation, and an increase in overall survival. Primary tissue from leukemia patients also required Stau2 for continued growth, suggesting a conserved function for Stau2 in tumor development and progression.

“We are particularly excited about this work because, to our knowledge, this is the first demonstration that Staufen2 is a key dependency in any cancer,” said Reya, who is a member of Moores Cancer Center and the Sanford Consortium for Regenerative Medicine.

To understand the molecular details of how Stau2 is important in tumor cell proliferation, the researchers looked at its binding partners and interactors by RNA-Seq and eCLIP-seq and found that Stau2 regulates important oncogenes (Ras), epigenetic factors and chromatin remodellers such as histone demethylases. Most of these are potential drug targets and hence any information on their regulation helps design better therapies.

“This work will be particularly important for the discovery of new treatments. Our genome-wide screen identified cellular signals critical for the growth of cancer, and in the future, this study will be useful to study the microenvironment, the area around the tumor that includes tissue, blood vessels and important molecular signals related to how the cancer behaves,” first author, Dr.Jeevesha Bajaj sums up the study.

Related Article: Evolved Cas9 Facilitates CRISPR Access to Previously Unexplored Genomic Sites

References
  1. https://www.nature.com/articles/s43018-020-0054-2#article-info
  2. https://ucsdnews.ucsd.edu/pressrelease/finding-leukemias-weakness-using-genome-wide-crispr-technology
  3. https://www.urmc.rochester.edu/news/story/5642/researchers-find-new-leukemia-genes-using-crispr-technology.aspx

 

©www.geneonline.com All rights reserved. Collaborate with us: [email protected]
Related Post
The Latest Talk in Cancer Immunotherapy: A Brief Overview of Developments & Current Players in the Exosome Space
2025-04-23
From Cancer to Cosmetics, Physiological to Pathological – The Field of Exosomes Full of Endless Opportunities
2025-04-22
NGS
New Philippines NGS Center Targets Critical Gaps in Genomic Care
2025-03-31
LATEST
World Vaccine Congress Washington 2025 Recap: Urgent Calls for Trust, Tech, and Global Access
2025-04-25
Astellas’ Transformation Journey: From Merger to Global Player, Betting on the Edge of Innovation and Risk?
2025-04-25
Roche Announces Massive 50 Billion Dollar Investment in the United States
2025-04-25
Steminent Stands Ready to Showcase Novel MSC-based Therapy for Spinocerebellar Ataxia at Global Stage
2025-04-24
Arkansas Medicaid Work Requirements Led to Coverage Loss for a Significant Number of Recipients
2025-04-24
Boehringer agrees new partnership to advance first-in-class precision cancer therapies
2025-04-24
Bristol Myers Squibb Schizophrenia Drug Fails Pivotal Test as an Add-On to Antipsychotics
2025-04-24
EVENT
2025-04-25
AACR Annual Meeting 2025
Chicago, U.S.A
2025-05-03
29th Taiwan Joint Cancer Conference 2025
Taipei, Taiwan
2025-05-05
Swiss Biotech Day 2025
Basel, Switzerland
2025-05-13
ASGCT 28th Annual Meeting 2025
New Orleans, U.S.A.
2025-05-30
ASCO Annual Meeting 2025
Chicago, U.S.A
2025-06-11
ISSCR 2025 Annual Meeting
Hong Kong
Scroll to Top