New genetic target for blood cancer treatment

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Aligning a pathway essential to the survival of certain types of acute myeloid leukemia could represent a new therapeutic option for patients, according to the latest research.

Researchers at the Wellcome Sanger Institute found that a specific genetic mutation linked to poor prognosis for blood cancer, when combined with other mutations in mice and human cell lines, is involved in the development of the disease.

The study published today (April 30) in Nature Communications provides a better understanding of how the loss of function mutation in the CUX1 gene leads to the development and survival of acute myeloid leukemia. The results suggest that targeting a pathway that is essential for the continued growth of these cancer cells could lead to new targeted therapies for some patients.

Acute myeloid leukemia (AML) is an aggressive blood cancer that affects people of all ages and often requires months of intensive chemotherapy and lengthy hospital admissions. It typically develops in cells in the bone marrow to displace the healthy cells, which in turn leads to life-threatening infection and bleeding. Current AML treatments have remained unchanged for decades, and less than one in three survives the cancer.

Previously, researchers at the Wellcome Sanger Institute, through large-scale DNA sequencing analysis, found that dysfunctional mutations in the CUX1 gene on chromosome 7q were seen in various cancers, including AML, where they are linked to a poor prognosis. However, the role of this gene in AML development is unclear.

In this new study, the team used CRISPR / Cas9 gene editing technology to show that a lack of working CUX1 leads to the expansion of certain types of blood stem cells that are defective in a type of regulated cell death known as apoptosis are. They found that the loss of CUX1 caused increased expression of the CFLAR gene – which encodes a protein that inhibits apoptosis – and may provide a means for mutated cancer cells to evade cell death and multiply. The researchers showed that targeted treatment for CFLAR, or apoptosis escape routes in general, could be a potential treatment for those living with this type of AML that has been linked to a poor prognosis. There are currently no clinically approved drugs for CFLAR.

Dr. Saskia Rudat, co-first author and Postdoctoral Fellow at the Wellcome Sanger Institute, said: “By further exploring the role of CUX1, we now have new insights into how this gene and its lack of mutation play a key role in blood cancer cell survival. While this mutation does not appear to cause the development of malignancies alone, focusing on the signaling pathways associated with CUX1 is a good target for further research. “

Dr. Emmanuelle Supper, Co-First Author and Postdoctoral Fellow at the Wellcome Sanger Institute, said, “This research has allowed us to gain vital information about the evolution of this disease and would not have been possible without the new and exciting CRISPR / Cas9 and genome sequencing technologies that allow us to study genetic weaknesses in cancer. Learning about the genetic basis of disease and how multiple mutations come together to cause blood cancer is vital if we are to save lives in the future. “

Dr. Chi Wong, Senior Author and Wellcome Clinical Fellow at the Wellcome Sanger Institute and Honorary Consultant Haematologist at Addenbrooke’s Hospital, said, “Acute myeloid leukemia is a devastating disease that is currently difficult to treat, especially in cases caused by genetic lesions such as these new study provides evidence that could help develop a new targeted treatment for some people with acute myeloid leukemia and offers hope for this group of patients who, unfortunately, have a poor prognosis. ”

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More information:
Nature Communications (2021). DOI: 10.1038 / s41467-021-22750-8 Provided by the Wellcome Trust Sanger Institute

Quote: New Genetic Target for the Treatment of Blood Cancer (2021, April 30), accessed April 30, 2021 from

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