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    SEPTEMBER 23, 2004
 
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Gene expression in lymphoid cells can determine lymphoma cancer


Giordano

Analyzing the expression levels of the gene CDK9 (cyclin-dependent kinase) and its attached molecule CYCLIN T1 in lymphoid cells in a sample of blood can accurately pinpoint lymphoma, according to researchers at Temple’s Sbarro Institute for Cancer Research and Molecular Medicine and the human pathology and oncology department at the University of Siena in Italy.

Their study, “CDK9/CYCLIN T1 expression during normal lymphoid differentiation and malignant transformation,” appeared in the Journal of Pathology.

Lymphomas are generally difficult to diagnose since no single test currently exists to sufficiently establish their presence. Clinical practice often revolves around a pathologist looking for changes in normal lymph node architecture and cell characteristics through a series of tests, such as blood tests, X-rays, computerized tomography scans, magnetic resonance imaging and bone marrow biopsy.

“There are many types and subtypes of lymphoma, some of which are easy to detect, but many that are very difficult to identify,” said Antonio Giordano, director of the Sbarro Institute and one of the study’s principal investigators.

The researchers found that by taking a sample of blood and doing immunohistochemical analysis for the expression of CDK9 and CYCLIN T1, they were able to accurately pinpoint the type of lymphoma — Hodgkins or non-Hodgkins — as well as its stage of advancement. Non-Hodgkins lymphoma is the sixth-most common cancer in the United States.

“Basically, this new method is a very powerful tool in determining the presence of cancer by analyzing these two molecules in the lymphoid tissue,” said Giordano, an internationally recognized researcher in the genetics of cancer and gene therapy. “The change of levels of CDK9 and CYCLIN T1 in lymphoid cells shows a correlation with activity of the cancer. The higher the expression of the gene and the attached molecule in the blood sample, the more likely for lymphoid cancer.”

CDK9 was originally isolated by Giordano, who at the time was a researcher in Temple’s Fels Cancer Institute, and his team in 1992. A member of a family of kinases, CDK9 was originally referred to as PITALRE, the name of the amino acid sequence that is similar in all members of this kinase family.

“We were screening a human DNA library in order to look for members of this family, and we found CDK9, a gene that encodes for a protein that has the size of 43 kilodaltons,” says Giordano, who is also co-director of the Center for Biotechnology in the College of Science and Technology.

Over the next 10 years, CDK9 would prove to be a “multifunctional” gene, playing many different roles. According to Giordano, among the many functions of CDK9 that have been discovered, one of the most interesting is the role of this kinase in cellular differentiation, particularly muscle differentiation.

“In practical terms, when we overexpress this protein, we are able to promote myogenic differentiation by enhancing the myoD function,” said Giordano, who also discovered the tumor-suppressing gene Rb2/p130. “Our studies have demonstrated that in human tissue, CDK9 is a very important player in specialized tissue, as we see in this study with lymphoid tissue.”

Clinical work for the study was coordinated by Giordano and performed at the human pathology and oncology department at the University of Siena in collaboration with professors Lorenzo Leoncini and Piero Tosi. The researchers believe that this unique method of using the immunohistochemical analysis of a blood sample for the expression of CDK9 and CYCLIN T1 will become an important diagnostic tool in the battle against lymphoma.

The study was supported by the Italian Ministry for Education, Universities and Research and Sbarro Health Research Organization, National Institutes of Health and Petruccelli–American Italian Research Scholarship.

- By Preston M. Moretz

 

 


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