Understanding how leukemia and lymphoma cells resist treatment

April 12, 2018 by Anne-Marie Beauregard, University of Montreal
Jennifer Fraszczak, Charles Vadnais, Riyan Chen et Tarik Möröy. Credit: IRCM

In a study published in Nature Communications, a team led IRCM Hematopoiesis and Cancer Research Unit director Tarik Möröy reveals how the GFI1 protein sometimes helps leukemia and lymphoma cancer cells evade therapy. This discovery could eventually help orient patients towards more effective treatment by considering the particular characteristics of their disease.

In this Q&A, Möröy and his team offer an overview of their findings.

What is this research project about?

One of our goals is to understand more precisely the mechanisms involved in the response to treatments designed for leukemia and lymphoma, two cancers linked to overproduction of . Although we understand the main mechanisms of these diseases, we are still missing many of their subtleties.

How do most cancer treatments work?

Cancer multiply quickly and in a way that is out of control; this is how tumours are formed. The goal of cancer treatments is to destroy these cells. In order to achieve this, doctors use radiotherapy and chemotherapy, which damage the DNA of the cancer cells, thereby destroying them or preventing them from multiplying.

In this study, we were interested in a protein that plays a role in the development of leukemia and lymphomas, the GFI1 protein. We already knew that it could affect the survival of cancer cells following treatments, but we did not understand how. We wanted to grasp GFI1's role in this dynamic. In order to accomplish this, we conducted experiments on mouse models and cultures of .

Why is it important to understand how these treatments work?

Thanks to scientific advances, therapeutic options such as radiation and chemotherapy are now available to stop leukemia and lymphoma, and they often lead to remission. However, these treatments can have severe side effects, and they sometimes prove to be ineffective. By gaining more knowledge about them, we could more effectively direct each patient to the therapy that best suits him or her. A personalized would increase the chances of success, while reducing unnecessary side effects.

What did your research reveal?

Our study shows that the GFI1 protein interacts with an enzyme, PRMT1, which, in turn, chemically modifies and activates proteins responsible for repairing DNA breaks. This new function for GFI1 is a new piece of the puzzle to understand how cells repair their DNA.

Ordinarily, GFI1 is necessary for the repair of . The problem is that GFI1 is often overexpressed in cancer cells: in these cases, GFI1 can help them resist certain treatments, since GFI1 helps to repair DNA breaks caused by radiotherapy or chemotherapy.

Could this study lead to therapeutic advances?

Ultimately, we hope this research will lead to even more effective decision-making in the clinical setting. For example, patients could be referred to the most appropriate treatment according to the level of GFI1 activity in their . It could also be possible to make tumours more sensitive to these treatments by targeting the mechanisms of DNA repair affected by GFI1.

Finally, we hope that the principles presented in this study will also be applicable to other types of tumours in which we suspect GFI1 to be involved, including such as medulloblastomas, the most common and most dangerous type of brain tumour in children. Sometimes scientific research appears to address a narrow field, but its repercussions can extend well beyond.

Explore further: Study suggests improved treatment alternative for lymphoid leukemia

Related Stories

Study suggests improved treatment alternative for lymphoid leukemia

February 11, 2013
Discovering what they call the "Achilles' heel" for lymphoid leukemia, an international research team has tested a possible alternative treatment that eradicated the disease in mouse models.

Overlooked DNA shuffling drives deadly paediatric brain tumour

June 23, 2014
One of the deadliest forms of paediatric brain tumour, Group 3 medulloblastoma, is linked to a variety of large-scale DNA rearrangements which all have the same overall effect on specific genes located on different chromosomes. ...

'Virtual tumours' predict success of tumour-heating sound waves

March 28, 2018
Researchers have developed a virtual, computerised cell model that is being used to predict the success of treating cancer with an exciting new tumour-heating technology – which uses targeted sound waves to heat and destroy ...

Targeting breast cancer through precision medicine

January 9, 2018
University of Alberta researchers have discovered a mechanism that may make cancer cells more susceptible to treatment. The research team found that the protein RYBP prevents DNA repair in cancer cells, including breast cancer.

Study explores impact of obesity on bone marrow cells

December 27, 2017
New research published in the Journal of Experimental Medicine highlights the pernicious effect of obesity on the long-term health of blood-making stem cells (hematopoietic stem cells).

Recommended for you

RNA thought to spread cancer shows ability to suppress breast cancer metastasis

October 22, 2018
Researchers at The University of Texas MD Anderson Cancer Center have discovered that a form of RNA called metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) appears to suppress breast cancer metastasis in mice, ...

Revealing the molecular mystery of human liver cells

October 22, 2018
A map of the cells in the human liver has been created by University Health Network Transplant Program and University of Toronto researchers, revealing for the first time differences between individual cells at the molecular ...

Targeting a hunger hormone to treat obesity

October 22, 2018
About 64 per cent of Canadian adults are overweight or obese, according to Health Canada. That's a problem, because obesity promotes the emergence of chronic diseases such as type 2 diabetes, heart disease and some cancers.

New tool gives deeper understanding of glioblastoma

October 22, 2018
Researchers in the lab of Charles Danko at the Baker Institute for Animal Health have developed a new tool to study genetic "switches" active in glioblastoma tumors that drive growth of the cancer. In a new paper in Nature ...

Pancreatic cancer genetic marker may predict outcomes with radiation therapy

October 22, 2018
Pancreatic cancer is one of the most difficult cancers to treat and is a leading cause of cancer-related deaths. Now, Sidney Kimmel Cancer Center—Jefferson Health and Lankenau Institute for Medical Research scientists find ...

New drug combination destroys chemo-resistant blood cancer

October 22, 2018
Researchers from The Ottawa Hospital and the University of Ottawa have developed a promising targeted strategy to treat chemotherapy-resistant acute myeloid leukemia (AML) and a diagnostic test to determine which AML patients ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.