Acute Myeloid Leukemia Induces Bone Marrow Failure by Inhibiting Production of Hematopoietic Stem Cells
Scientists studying acute myeloid leukemia (AML) have discovered that rather than displacing hematopoietic stem cells in the bone marrow as previously believed, the cancer is in fact inhibiting production of downstream hematopoietic cells, effectively putting them to sleep. The findings were published recently in Proceedings of the National Academy of Sciences.
The finding offers the possibility that these stem cells could somehow be turned back on, offering a new form of treatment for AML. The work was led by scientists at Queen Mary, University of London, with the support of Cancer Research UK’s London Research Institute.
Study Details
The scientists studied the levels of hematopoietic stem cells in the bone marrow of mice transplanted with human AML. They found the numbers of normal mouse hematopoietic stem cells stayed the same, but what did change was that the stem cells were no longer going through the stages of development that finally result in the formation of new blood cells.
Once the cells were removed from the leukemic environment, residual normal hematopoietic cells differentiated normally and outcompeted steady-state hematopoietic cells, indicating that the effect is reversible.
The findings were confirmed by the analysis of bone marrow from 16 patients with AML.
David Taussig, PhD, from the Barts Cancer Institute at Queen Mary, University of London, who led the research, said, “The widely accepted explanation has held that AML causes bone marrow failure by depleting the bone marrow of normal hematopoietic stem cells by killing or displacing them.
“However, we have found that samples of bone marrow in both mice models and patients with AML contain the same, or more, of these normal stem cells than usual. So the cancer isn’t getting rid of them, instead it appears to be turning them off so they aren’t going on to form healthy blood cells,” he said.
Important Step Forward
“If we can find out how the cancer cells are doing this, we can look at exploiting it to find ways to wake these stem cells up. This is very important as, while the cure rate for younger patients can be around 40%, in older patients it is much lower. The treatments we have, such as chemotherapy and bone marrow transplants, just aren’t very successful in this older patient group.”
Peter Johnson, MD, FRCP, Cancer Research UK’s Chief Clinician, said, “Although major progress has been made in treating AML over the years, there’s still an urgent need for more effective treatments to improve long-term survival. This study takes us an important step forwards in our understanding of what’s going on in the bone marrow of people with AML, an area that we have not known enough about previously, and the challenge now is to turn this understanding into new treatments for patients.”
Dr. Taussig added, “Usually when the body is stressed, the stem cells become very active. For example, if you have a hemorrhage, they will jump into action to produce more new blood cells. The cancer cells are somehow overriding this, and our next phase of work will concentrate on how they are doing this.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
