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Unexpected cell key to the recurrence of blood cancer

11 September 2018 15:20

Researchers at McMaster University have provided evidence of new cancer cells, which they called regenerative cells that are responsible for the return of acute myeloid leukemia after remission.

Current therapy is effective in inducing remission in adult patients with acute myeloid leukemia, but the majority of patients die after relapse. It is believed that this is caused by a relapse and inactive rare cancer stem cells that avoid chemotherapy.

The study, published today in the journal Cancer Cell, suggests that leukemia cells change in unique ways in response to chemotherapy, allowing them to hide in a short time, so they can start the regeneration of the disease.

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The study involved a joint effort of both scientists and physicians and covers more than five years. The team took on the task of hunting for rare leukemia cells that remain after chemotherapy. The surprise was that the most resistant cells remaining after the treatment, do not fit a profile of cancer stem cells.

"Many cancer researchers, including our team thought it was dormant cancer stem cells that can resist chemotherapy, which continue to cause a relapse," - said Mick Bhatia, lead author and director of the McMaster research institute.

Bhatia said that so far the initial effects immediately following treatment with chemotherapy have been largely unexplored, because the remaining leukemia cells in the body is easy to hide and go unnoticed amid the chaos caused by the therapy itself.

"Chemotherapy is not entirely specific and destroys many other tissues, making the patient's body is a difficult place to research to find the cells responsible for relapse," - he said.

"It's like trying to find a needle in a haystack. We try to find what is causing the recurrence somewhere where chemotherapy has caused great collateral damage. "

To overcome these obstacles, the team turned to a model where installed leukemia in laboratory mice, and chemotherapy can be administered in accordance with the way patients are treated at the clinic.

"This allowed us to nullify several human leukemia cells that survive, because we could easily distinguish them from atypical cells of the mouse," - said Lily Aslostovar, study co-author and postdoc from Stem Cell McMaster and Research Institute of Cancer. "Finally, we were able to give details of what is happening in this transitional period before a relapse."

The main conclusion of the team was to determine the moment when the disease is replicated, becoming very regenerating, creating conditions for a possible relapse. It offered a new way to identify the masked cancer cells, which are hidden in the bone marrow of patients with leukemia shortly after chemotherapy. It is important to note that similar patterns of regeneration of leukemia can be seen across the spectrum of different subtypes of patients, providing a common thread to guide the development of new treatments at a critical moment after the chemotherapy.

"This is a great clinical opportunity, because this type of leukemia is very diverse and responds differently to patients," - says Alison Boyd, co-author of the study.

"In the clinical setting has been difficult to find a common therapeutic target in a wide range of patients, and these regenerative cells provide this similarity," - she said.

The researchers hope that this new understanding of leukemic recovery process will give doctors the opportunity to introduce additional products in combination with chemotherapy. This will allow to take advantage of the benefits of chemotherapy at the same time opposing its shortcomings, targeting these altered cancer cells, Bhatia said.

"We were impressed by the fact that the disease seems to be very weak after chemotherapy because the cancer stem cells have been largely eliminated," - Boyd said. "We believe that there are opportunities, because we now have a window where we can hit the cancer until it does not work."

Bhatia said that the study results support the continuation of this new emerging hypotheses about the causes of cancer recurrence, which is partly due to the response to chemotherapy and is likely to be applied to additional cancers other than leukemia.

"Chemotherapy has increased the number of years of life of cancer patients, but if you look at the overall mortality rate among people with leukemia, they are relatively not changed", - said Bhatia. "The problem is that the tumor returns. This recurrence that kills patients. Our goal - to prevent a relapse. "

Source: https://www.sciencedaily.com/releases/2018/09/180910142512.htm

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