Red blood cells
Preclinical research has revealed a treatment that might preserve normal hematopoietic function in patients with acute myeloid leukemia (AML).
Researchers found that AML suppresses adipocytes in the bone marrow, which leads to imbalanced regulation of endogenous hematopoietic stem and progenitor cells and impaired myelo-erythroid maturation.
However, a PPARγ agonist can induce adipogenesis, which suppresses AML cells and stimulates the regeneration of healthy blood cells.
Researchers reported these findings in Nature Cell Biology.
The team found that adipocytes in the bone marrow support myelo-erythroid maturation of hematopoietic stem and progenitor cells. But AML has a negative effect on the maturation of adipocytes, which explains why deficient myelo-erythropoiesis is “a consistent feature” of AML.
The researchers also found that pro-adipogenesis therapy—treatment with the PPARγ agonist GW1929—protects healthy myelo-erythropoiesis and limits leukemic self-renewal.
“Our approach represents a different way of looking at leukemia and considers the entire bone marrow as an ecosystem, rather than the traditional approach of studying and trying to directly kill the diseased cells themselves,” said study author Allison Boyd, PhD, of McMaster University in Hamilton, Ontario, Canada.
“These traditional approaches have not delivered enough new therapeutic options for patients. The standard of care for this disease hasn’t changed in several decades.”
“The focus of chemotherapy and existing standard of care is on killing cancer cells, but, instead, we took a completely different approach, which changes the environment the cancer cells live in,” said study author Mick Bhatia, PhD, of McMaster University.
“This not only suppressed the ‘bad’ cancer cells but also bolstered the ‘good’ healthy cells, allowing them to regenerate in the new drug-induced environment. The fact that we can target one cell type in one tissue using an existing drug makes us excited about the possibilities of testing this in patients.”
“We can envision this becoming a potential new therapeutic approach that can either be added to existing treatments or even replace others in the near future. The fact that this drug activates blood regeneration may provide benefits for those waiting for bone marrow transplants by activating their own healthy cells.”
