Blood Cancer Therapy Could Accelerate Immune Aging

Autologous bone marrow transplants, commonly used to treat blood cancer, may age the immune system by up to 30 years

While cancer treatments are preferable to the alternative, many of them come with significant side effects. Of these therapies, bone marrow transplants are often extremely effective and unavoidable, but research is suggesting there may be a drawback to the procedure. 

What are bone marrow transplants?

Bone marrow transplants typically involve the destruction of existing bone marrow cells through a range of interventions like chemotherapy, before replacing them with a new bunch of cells. These new cells can either be produced from the patient's own healthy cells (autologous), or taken from another and transplanted (allogeneic). Bone marrow transplantation is highly effective, but is also dangerous with a high mortality rate and risk of rejection. 

A lifeline with a cost

A team from the University of Carolina examined molecular markers in the immune cells of 63 patients who had undergone an autologous or allogeneic bone marrow transplant for myeloma, lymphoma or leukemia. They discovered that levels of mRNA (a measure of gene expression) of a protein called p16 were unusually high in T-cells from those who had undergone an autologous transplant; in fact 3 times above the level they were before transplantation, which translates to approximately 30 years of aging, at least when it comes to p16 expression. Levels were also higher in allogeneic transplant patients, but the increase was less significant. T-cells are a specific type of immune cell. 

Research has determined that cytotoxic chemotherapy has a similar toll on the immune system, causing a doubling in p16 expression in some patients. p16 is a tumour suppressor gene that plays a role in halting the cell cycle, and is closely tied with the aging process, making it a reasonable measure of aging in certain tissues. p16 is also one of the best markers of cellular senescence that we have, and senescence increases as tissue gets older. 

"We know that transplant is life-prolonging, and in many cases, it's life-saving, for many patients with blood cancers and other disorders. At the same time, we're increasingly recognizing that survivors of transplant are at risk for long-term health problems, and so there is interest in determining what markers may exist to help predict risk for long-term health problems, or even in helping choose which patients are best candidates for transplantation"

Why could this be happening?

 Those undergoing an autologous transplant typically receive an additional round of chemotherapy, which could explain why levels of p16 are markedly higher again. The researchers also noted that a forced regeneration of the host's immune system from a transplant may have some side effects, including stress and accelerated aging. Stem cells are especially sensitive to their surroundings, and a shift in environmental cues could well have severe consequences to healthy maintenance. These cells must also divide a great deal to replenish the marrow, which in itself may have consequences.  

Human cells with acute myelocytic leukemia (AML). Credit; National Cancer Institute

"Many oncologists would not be surprised by the finding that stem cell transplant accelerates aspects of aging. We know that years after a curative transplant, stem cell transplant survivors are at increased risk for blood problems that can occur with aging, such as reduced immunity, increased risk for bone marrow failure, and increased risk of blood cancers. What is important about this work, however, is that it allows us to quantify the effect of stem cell transplant on molecular age"

Can we do anything about this? 

Aside from choosing appropriate candidates, we'll have to conduct more study into exactly what's going on in these cells and whether certain treatments can rejuvenate these patients by removing senescent cells for example. It's important to note that that while p16 is a good marker of age, because these are unusual cellular circumstances it's not clear how this affects immune cell function. These cells may remain young in other respects, but this wasn't tested in depth.  

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