Canadian Scientists Discover How to Prevent Relapse of Acute Myeloid Leukemia

A group of researchers from McMaster University in Canada has identified a new type of cancer cell, identified as regenerative, responsible for the relapse of acute myeloid leukemia after remission.

The current anti-tumor methods are quite successful in achieving remission in people with acute myeloid leukemia. However, most patients still die later due to relapse. It was previously believed that the return of the disease was triggered by rare "dormant" cancer stem cells that managed to evade chemotherapy. But this hypothesis has recently been called into question.

The results of the study, published last week in the peer-reviewed journal Cancer Cell, indicate that leukemia cells can uniquely transform in response to chemotherapy: this allows them to temporarily disguise themselves and subsequently initiate the process of disease resurgence.

The study, conducted through the combined efforts of scientists and medical professionals, lasted more than five years. The team aimed to identify rare leukemia cells that remain in the body immediately after chemotherapy treatment. To their surprise, researchers found that most of the surviving cells exposed to toxins had a genetic profile different from malignant cells. "Many oncology researchers, including our team, have always thought that the main culprits are the 'dormant' cancer stem cells that can withstand chemotherapy and provoke relapse in the future," says Mick Batty, the lead author of the project and head of the Stem Cell and Cancer Research Institute at McMaster University.

He noted that until now, the primary consequences of chemotherapy, manifesting immediately after treatment, had remained unidentified because the surviving leukemia cells easily mixed with other cells in the body, remaining invisible in the chaos created by the treatment. "Chemotherapy has low specificity and – along with malignant cells – destroys many other tissues, creating disorder in the body and complicating the detection of the cells responsible for relapse," explains Mick Batty. "It's like trying to find a pen of unknown shape and size in a room destroyed by a bomb."

To overcome these obstacles, the research team created a mouse model, transplanting human leukemia cells and administering chemotherapy – just as patients are treated at the clinic. "This allowed us to detect several surviving human tumor cells because they were easily distinguishable from healthy mouse cells," says co-author of the study Lily Aslostovar. "We finally managed to understand what happens during this transitional period before relapse occurs."

The main task of the scientists was to establish the moment when cancer begins to revive, preparing the ground for subsequent relapse. This provided them with new opportunities to identify the masked tumor cells that had taken refuge in the bone marrow of leukemia patients after "chemotherapy." Notably, similar mechanisms of leukemia resurgence were observed in different patients, indicating a common principle that should underlie new therapeutic methods to be applied at a critically important moment – immediately after chemotherapy.

This data opens up extraordinary possibilities for physicians, as this type of leukemia has many variations and responds differently to treatment in each specific patient. "In clinical settings, it has been difficult to find commonalities among all types of leukemia to determine a therapeutic target for most patients, and these 'regenerative' cells are that commonality," concludes one of the study's authors.

The researchers hope that the new understanding of the leukemia resurgence process will enable oncologists to include additional anti-tumor drugs in the treatment regimen, combining them with chemotherapy agents. "This will enhance the benefits of chemotherapy treatment while simultaneously neutralizing its drawbacks by specifically targeting altered cancer cells," says Professor Batty.

According to the researchers, they were astonished by how weakened the disease was after chemotherapy when most of the stem cancer cells were destroyed. "We believe this opens up the possibility for us to ultimately conquer blood cancer, as we now know its weak point," concludes one of the experiment's authors.

The scientists believe that the results of their study will serve as a basis for further development of a new hypothesis regarding the causes of cancer recurrence in cases partially related to the response to chemotherapy, and may possibly be applicable to other oncological diseases, not just leukemia.

"Chemotherapy allows for extending the lives of cancer patients, but if we look at the overall mortality statistics among people with leukemia, it remains virtually unchanged," says Professor Batty. "The main problem is that the disease returns over time. People die specifically from relapse. Therefore, our goal is to prevent the re-emergence of cancer."