Gene Identified that Promotes Bone Lesions in Multiple Myeloma

Gene Identified that Promotes Bone Lesions in Multiple Myeloma

According to a recent article published in The New England Journal of Medicine, overexpression of the gene referred to as dickkopf1 (DKK1), is associated with a type of bone lesion in multiple myeloma.

Multiple myeloma is a cancer involving important immune (infection-fighting) cells called plasma cells. Plasma cells aid the body in fighting infection by producing specialized proteins called antibodies that have the ability to target and/or kill foreign cells. In multiple myeloma, cancerous plasma cells produce abnormal and excessive antibodies that do not have the ability to properly fight infection. In addition, the cancerous plasma cells accumulate in the bone marrow, suppressing the normal formation and function of other cells that are necessary for normal production of blood cells and immune functions. In addition, multiple myeloma is associated with breakdown of the bone associated with bones being broken down faster than they are being repaired.

The integration of genetics into the clinical setting has been an area of much focus. One of these areas has been the evaluation of several genes and the association of combinations of several genes as indicators of patient outcomes. It is believed that one main reason behind the differences in response rates and survival rates among patients with the same type and extent of cancer who are treated with the same therapeutic regimen is the differences in gene expression of individual cancers. Therefore, identifying and understanding which genes are associated with particular outcomes, or sensitivity to specific therapies, will help individual treatment options, sparing patients from treatment that does not provide benefit, and optimizing overall treatment choices.

Bones are constantly breaking down and re-forming themselves through complex biological signaling systems. Patients with advanced multiple myeloma often have impaired signaling processes in regards to bone maintenance, and suffer from the breaking down of bone that is not properly repaired or replaced with new bone. These areas of bone are referred to as osteolytic lesions, and are sites at which bone fractures may occur. However, researchers have been evaluating why some patients with advanced multiple myeloma suffer from osteolytic lesions and some patients never experience osteolytic lesions.

Recently, researchers from the University of Arkansas performed gene expression profiling in an attempt to uncover the expression of one or more genes that may be associated with the development of osteolytic lesions in patients with multiple myeloma. These researchers performed genetic analyses on over 10,000 genes in nearly 200 patients with multiple myeloma with or without osteolytic bone lesions, and 45 healthy individuals. Through genetic analysis, 57 genes were identified that had a possible association with the development of osteolytic bone lesions. Of these 57, researchers narrowed down the gene to DKK1, which is known to play a role in the signaling of bone formation. DKK1 levels were elevated in bone marrow and peripheral blood samples of patients with osteolytic bone lesions.

The researchers concluded that the overexpression of DKK1 in multiple myeloma cells appears to be significantly associated with the development of osteolytic bone lesions in patients with advanced multiple myeloma. Research is now underway to develop a drug that is able to reverse the overexpression of DKK1, so that osteolytic lesions may be prevented in multiple myeloma. In addition, the researchers suggested that treatment with bisphosphonates, agents used for the treatment or prevention of cancer spread to the bone, may be beneficial for patients with elevated levels of DKK1. Patients with multiple myeloma may wish to speak with their physician about the risks and benefits of testing for DKK1 levels.

Reference: Tian E, Zhan F, Walker R, et al. The Role of the Wnt-Signaling Antagonist DKK1 in the Development of Osteolytic Lesions in Multiple Myeloma.

The New England Journal of Medicine. 2003;349:2483-2494.

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