Researcher Looks for Link Between Protein and Hodgkin Lymphoma

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One Year Research Update:

Maxwell Krem, MD, PhD is a CureSearch Young Investigator studying Hodgkin lymphoma at the University of Washington. His research specifically examines the effect of a particular protein called KLHDC8B on the development of Hodgkin lymphoma. When normal cells replicate, they produce this protein, which acts as a protective shield in the cell. Dr. Krem’s early research revealed that when this particular protein is deficient, cells are more likely to take on the properties of Hodgkin lymphoma cells. He hypothesized that the absence of the protein contributed to the spread of the disease, and that the protein itself might protect against the development of lymphoma.

In his first year of research, Dr. Krem tested his conjecture that the KLHDC8B protein might function as a “tumor suppressor” and a protector of healthy cells. To test this, he bred mice that were missing this special protein to determine if they were more likely to develop lymphoma or not. Then he examined what happened in their blood and bone marrow when this protein was absent. Dr. Krem found that the bone marrow activity of the mice changed, but it did not increase cancerous activity. This result means that the absence of the protein KLHDC8B is only one factor in the development of the disease.

Although the special protein did not turn out to be as significant as Dr. Krem originally thought, the results of this study are still important because they show that Hodgkin lymphoma has “genetic heterogeneity.” This means that multiple different mutations can lead to Hodgkin lymphoma. This diversity means that researchers are unlikely to find a “magic bullet” treatment. As he moves forward with his research, Dr. Krem plans to examine the mouse tissue more closely and test other genes that may contribute to the growth of Hodgkin lymphoma. Although the KLHDC8B protein did not prove to be strongly protective, this study revealed valuable insight into how Hodgkin lymphoma develops and such discoveries are crucial for developing more effective treatments.

Maxwell Krem, MD, PhD, from The University of Washington strives to treat his patients as he would want to be treated, delivering state-of-the-art medical therapy. This desire led him to research the molecular genetics and pathogenesis of Hodgkin lymphoma, a cancer of the lymphoid system, which when it functions normally creates white blood cells whose job is to fight infection and disease.

Approximately 900 children under age 19 are diagnosed with Hodgkin lymphoma each year, the majority of whom are teenagers ages 15 – 19. Dr. Krem hopes that his research will lead to targeted therapies and a better understanding of Hodgkin lymphoma.

Researchers believe that Hodgkin lymphoma is caused by a mutated cell called Reed-Sternberg (RS). This cell, for reasons not yet understood, recruits healthy cells to cluster around it, creating a tumor. Unlike other types of cancer, only about 1% of cells in the Hodgkin lymphoma tumor are actually cancerous.

Maxwell Krem
  • Maxwell Krem, MD, PhD
  • Acting Instructor, Division of Medical Oncology
  • University of Washington

A normal cell has one nucleus with 46 chromosomes inside of it. Unlike normal cells, RS cells have two or more nuclei. When two nuclei are present, there are often gained or lost chromosomes. In 2009, a family in which several people had Hodgkin lymphoma was studied, and a chromosomal translocation was found, meaning that pieces of a specific chromosome were broken off and placed on a different chromosome. When this happens, the cells reproduced abnormally, leaving out a specific protein (KLHDC8B) necessary for normal cell reproduction. Imagine trying to a read and understand that book if the chapters were printed out of order. What happens in the story would not make sense.

Dr. Krem is studying how the lack of protein KLHDC8B helps create abnormal cellular growth that leads to Hodgkin lymphoma. To conduct his research, Dr. Krem will study mice that are bred without this protein which develop Hodgkin lymphoma to determine how the RS cell creates a tumor and if the RS cells are able to reprogram the non-cancer cells around it to become cancerous.

Dr. Krem is funded for his research for two years by CureSearch for Children’s Cancer and will begin his work in 2013. During the course of his research, CureSearch looks forward to sharing Dr. Krem’s progress.

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