Canadian Scientists Discover How to Prevent Relapse of Acute Myeloid Leukemia

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

The current anti-tumour 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 thought that the return of the disease was triggered by rare "dormant" cancer stem cells that managed to evade the effects of 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 recurrence.

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 treatment with chemotherapeutic agents. To their surprise, researchers found that most of the surviving cells exposed to toxins had a different genetic profile 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, which manifest immediately after treatment, had remained undetected because the surviving leukemia cells easily blended in with other cells in the body, remaining invisible in the chaos created by the treatment. "Chemotherapy has low specificity and – alongside 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 that was transplanted with human leukemia cells and underwent chemotherapy – just as patients are treated in the clinic. "This allowed us to detect several surviving human tumour cells because it was easy to distinguish them 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 gave them new opportunities to identify the masked tumour cells that had chosen the bone marrow of leukemia patients as a hiding place 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 individual 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 authors.

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

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

Scientists believe that the results of their study will serve as a basis for further development of a new hypothesis about the causes of cancer recurrence in cases partially related to the response to chemotherapy, and may possibly be applied 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 recurrence of cancer."