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Blocking Hodgkin’s and Non-Hodgkin’s Lymphomas

September 09, 2015

Blocking Hodgkin’s and Non-Hodgkin’s Lymphomas

Background

By the end of this year, an estimated 556,000 people around the world will have received the devastating diagnosis that they have lymphoma. Nearly 305,000 more people will die from the disease.1

Lymphoma is a blood-cell cancer caused when DNA damages white blood cells that normally help fight off infections, and then die. Instead, the damaged cells go rogue to multiply and eventually form tumors in the lymphatic system that affect your lymph nodes, bone marrow, and spleen. Without aggressive and often debilitating chemotherapy and radiation treatments, the prognosis for lymphoma victims is grim. Thanks to groundbreaking research by a group of Boston-based scientists from Dana-Farber/Harvard Cancer Center, Boston University School of Medicine, and Brigham and Women’s Hospital, that diagnosis may someday be followed by a chemical cure.2

Cellular Sleuths

To appreciate fully the significance of recent advances in lymphoma research, a quick biology lesson is helpful. Humans are composed of billions of cells, each containing tens of thousands of genes. Genes are subsets of a chemical substance called DNA. These subsets make the specific proteins that cells need to control growth and how our bodies function. Infinitesimally small strands of chromosomes, also composed of DNA, carry these genes to regulate the cell activity. Most of us have 46 chromosomes that we inherit from our parents. Normally, this incredibly complex genetic orchestra goes on without a hitch… but, sadly, not always.3

Researchers recently discovered a disease-specific chromosome located on the short arm of chromosome 9 at position 24 (referred to as 9p24). Located on that same chromosome is the protein coding gene Janus kinase 2, or JAK2for short. JAK2is essential for controlling the production and growth of blood cells from stem cells. Scientists found that the duplication of mutated JAK2 genes increases their activity in two types of lymphoma, Classical Hodgkin’s lymphoma and primary mediastinal large-B-cell lymphoma, which comprises up to 40% of all non-Hodgkin’s lymphomas.

Eureka Moment

That earlier discovery led scientists from Dr. Margaret Shiff’s laboratory at the Dana-Farber Cancer Institute to evaluate the preclinical effects of a JAK2inhibitor known as fedratinib (SAR302503/TG101348). Through a combination of complex in vitro and in vivo procedures, the Boston-based researchers relied on PerkinElmer’s IVIS® SpectrumTM In Vivo Imaging System and Living Image® In Vivo Imaging Software to render detailed 3D images of mice clinically injected with human lymphoma and again following their treatment with the JAK2 inhibitor fedratinib.

Drawing on the IVIS Spectrum system’s ability to monitor disease progression, cell tracking, and gene expression, the research team succeeded in visually documenting that chemical JAK2 inhibition significantly decreases tumor growth for both Hodgkin’s Lymphoma and Large B-cell Lymphoma. Leveraging the bioluminescent imagery of the IVIS Spectrum platform, augmented by PerkinElmer’s Living Image® Software that simplifies image workflow, the Boston research team demonstrated for the first time that the JAK2 inhibitor also prolonged the survival of tumor-bearing animals significantly. Speaking for the entire team, lead researcher Yansheng Hao noted “these data prompt further consideration of chemical JAK2 blockade as a rational targeted therapy.4

References

  1. Bernard W. Stewart And Christopher P. Wildworld, Cancer Report, 2014. World Health Organization. Chapter 5.13. (http://www.scribd.com/doc/249125578/World-Cancer-Report-2014#scribd).
  2. Yansheng Hao, et. al., “Selective JAK2 Inhibition Specifically Decreases Hodgkin Lymphoma and Mediastinal Large B-cell Lymphoma Growth In Vitro and In Vivo,” Clinical Cancer Research, pp. OF1 – 10, May 15, 2014 (http://clincancerres.aacrjournals.org/content/early/2014/04/22/1078-0432.CCR-13-3007.full.pdf).
  3. Rare Chromosome Disorder Support Group, Understanding Chromosome Disorders: 9p24 Deletions, 2007 (http://www.rarechromo.org/information/Chromosome%20%209/9p24%20deletions%20FTNP.pdf).
  4. Yansheng Hao, et. al., “Selective JAK2 Inhibition Specifically Decreases Hodgkin Lymphoma and Mediastinal Large B-cell Lymphoma Growth In Vitro and In Vivo,” Clinical Cancer Research, pp. OF1 – 10, May 15, 2014 (http://clincancerres.aacrjournals.org/content/early/2014/04/22/1078-0432.CCR-13-3007.full.pdf).

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