GRAND RAPIDS – Scientists at Van Andel Research Institute have found a gene responsible for the development of pre-leukemia that could help lead to a cure.

The gene is called Drf1 could be crucial to the development of myeloproliferative disease and myelodysplastic syndrome, and only recently recognized as a form of cancer.

MPD and MDS are diseases of the bone marrow characterized by abnormal production of red blood cells and immune cells (white blood cells). MDS and MPD are usually accompanied by chronic anemia, requiring chronic blood transfusions. Some 30 percent of MDS cases progress to acute myeloid leukemia, a cancer of bone marrow cells. Other patients can develop a variant of this cancer, chronic myelomonocytic leukemia.

VARI researchers in the Laboratory of Cell Structure and Signal Integration, led by Senior Scientific Investigator Dr. Art Alberts, analyzed the effects of ?knocking out? the Drf1 gene, using molecular gene targeting to make sure the gene isn?t expressed.

“We focused on Drf1 because the human version of the gene is located in a specific genetic region associated with MDS and an increased likelihood of developing leukemias,” said Alberts.

In results presented last week to a scientific gathering at the Salk Institute in San Diego and published in two papers appearing in the journals Cancer Research and the Journal of Biological Chemistry, the VARI scientists found that Drf1 knockout leads to the inefficient production of red blood cells and an inability to make immune cells (white blood cells). The overall effects of knocking out the Drf1 gene are similar to those of MDS and MPS, suggesting that this gene may play a role in these diseases.

According to the American Cancer Society, which funded the studies along with the Van Andel Foundation and the National Institutes of Health (NIH), MDS and MPS are diagnosed in 10,000 to 15,000 patients each year. Most patients are over 60 years of age. Symptoms of MDS and MPS are varied and can include weight loss, fever, and loss of appetite. Since these symptoms may be caused by illnesses other than cancer, the full diagnosis must be made through the analysis of blood and bone marrow cells.

According to Alberts, the novel observations made at VARI may provide insight into how leukemias associated with MPD develop. Understanding if, where, and when defective Drf1 genes appear in MDS and MPD could help physicians predict the severity of the disease.

“There are several key unanswered questions we need to address,? said Alberts. ?Ultimately, our goal is to establish and use genetic models of MDS and MPS to test, evaluate, and improve upon current therapies for the disease.?

Experiments in collaboration with physicians at Spectrum Health in Grand Rapids have been initiated to address many of the questions that the new studies at VARI have raised. Future studies will examine how changes in the Drf1 gene in patients correlate with both the onset and the severity of the disease.

Lead authors of the two papers appearing in the Journal of Biological Chemistry and Cancer Research were Drs. Kathryn Eisenmann and Jun Peng; supporting VARI co-authors included Ms. Susan Kitchen and Mr. Rich West, Ms. Dagmar Hildebrand, and Dr. Robert Sigler. Additional co-authors and collaborators on one of the studies included Drs. Jinyi Zhang and Katherine Siminovitch of the Mt. Sinai Hospital at the University of Toronto, Canada.

For more information, click on VAI.Org

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