CRISPR helps find new class of leukemia genes

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Using CRISPR technology, scientists have discovered several new leukemia genes not previously known to have involvement in blood cancers, according to a new study.

The researchers then used the powerful new data to paint a clearer map for how aggressive leukemia arises and grows.

The paper in Nature Cancer points to several significant discoveries:

  • It unveils a new gene, Staufen 2 (Stau2), that regulates and drives the molecular programs for leukemia stem cells, those cells responsible for propagating the disease and for therapy resistance. Stau2 has been previously studied in the brain and nervous system but until now was not known to have a role in cancer.
  • The team used a tool called CRISPR, which allows scientists to edit DNA in cells and focus on large groups of genes active in a particular disease, in this case, myeloid leukemias. The paper shows that CRISPR can identify an entire class of gene mediators for leukemia, which will aid future research.
  • The team also tested its hypothesis in a mouse model designed to mimic the human experience with leukemia, instead of conducting studies solely in cell cultures, as several other groups have previously done.

Leukemia research is important because the survival rate is less than 10% for the most aggressive forms of the disease. In this case, investigators focused on chronic myeloid leukemia (CML), which targeted therapies, such as Gleevec, control well.

But CML becomes lethal when it advances or is diagnosed in an acute “blast” phase. The findings also have implications for acute myeloid leukemia (AML) and other blood cancers.

“This work will be particularly important for the discovery of new treatments,” says Jeevisha Bajaj, assistant professor of biomedical genetics at the University of Rochester Medical Center and a researcher at the Wilmot Cancer Institute.

“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.”

Before the team identified Stau2 and its essential function in leukemia, they discovered a broader group of RNA-binding proteins (RBPs), a family of genes that have recently started to be of interest in leukemia.

The researchers focused on a subset that had not been studied previously in any cancer, and found six of these RBPs abundantly expressed in human leukemia stem cells.

After further investigation of RBPs, Stau2 emerged as a critical regulator of the growth of CML in the blast phase, and AML.

Furthermore, researchers were able to delete Stau2 in laboratory experiments and show they could block the growth of cancer cells. The next step is to identify how to target Stau2 and other related genes for the benefit of patients.

Researchers from the University of California, San Diego School of Medicine contributed to the work. The American Society of Hematology, the National Cancer Center, and the National Institutes of Health supported the work.

Source: University of Rochester