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Leukaemia Cells Are “Bad to the Bone”
Leukaemia is a devastating disease that results in the disruption of normal blood production. Blood stem cells (hematopoietic stem cells or HSCs) give rise to all mature blood cells and maintain a balance of self-renewal and expansion. However, in this study, even when leukaemia is barely traceable in the blood, leukemic cells implant in the bone marrow and attack the body’s natural process of making healthy blood stem cells.
In this hematopoietic microenvironment, or niche, investigators have been searching for clues. In 2003 Doctor Laura M. Calvi introduced the concept that osteoblasts, which actively work to form bone in this same microenvironment, might have a key role in expanding and supporting the production of normal blood cells.
Benjamin J. Frisch, study author, began focusing on the impact of the leukaemia cells, which reside on the inside surface of bones adjacent to bone marrow activity. Until now no one had defined the important interactions that take place between leukaemia cells and osteoblasts (bone forming cells) and osteoclasts, which continually break down bone. Frisch and colleagues used a mouse model and human leukaemia tissue samples to show that: The way in which leukaemia alters the balance and cycles of osteoblast and osteoclast activity is complex and counterintuitive, and results in several measurable changes to the skeleton.
For example, since bone formation and bone resorption are usually tightly knit functions, researchers expected to see that dramatic bone loss due to leukaemia would also be consistent with a breakdown of bone and minerals, or resorption. Instead, they saw a mild increase in osteoclastic cells responsible for bone resorption, suggesting that leukaemia uncouples these two bone cell functions. Ultimately, researchers would like to understand more about osteoclasts during the disease process, so that they can perhaps target those cells for treatment.
In this study, leukaemia caused low-level and widespread bone thinning and bone loss, similar to osteoporosis, particularly in the long bones. Preliminary lab experiments showed that treatment with bisphosphonates, a commonly used class of drugs for people who suffer from bone loss, partially restored bone loss in mice with leukaemia.
Leukaemia results in the expression of a protein, known as CCL3, which slows bone formation. Thus, elevated CCL3 levels in leukaemia make it a tempting treatment target. Theoretically, newer drugs that block the CCL3 pathway might be able to restore the low-level, net loss of bone observed in many leukaemia patients. A few drug compounds that act on the CCL3 pathway are under study in early-stage clinical trials, Frisch said.
MEDICA.de; Source: University of Rochester Medical Centre