Feature

What is Hodgkin's Lymphoma disease and how can stem cells help?

by Wideacademy - 10 January, 2018

  • Lymphoma
  • Blood cancer
  • Bone Marrow
  • Stem Cell Transplant
  • Allogeneic
  • Autologous
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What’s is Hodgkin’s Lymphoma?

Both Hodgkin’s and Non-Hodgkin’s lymphomas are cancers of the blood that begin in a subset of white blood cells called lymphocytes.

If, in examining the cancer cells under a microscope, the doctor detects the presence of an abnormal cell called a Reed-Sternberg cell, the lymphoma is classified as Hodgkin’s.

Lymphocytes produce either B-cells (responsible for making antibodies to fight viruses) or T-cells, which destroy cells that have been taken over by viruses or become cancerous.

Abnormal lymphocytes become cancerous lymphoma cells, which multiply and collect in your lymph nodes eventually impairing your immune system.

The lymphatic system is composed of lymph nodes in our neck, armpits, groin, chest and abdomen. Lymphoma cancers develop in the nodes and can spread to the lymphatic tissues, such as the spleen, digestive tract and bone marrow. This is called primary extranodal disease.

Hodgkin’s lymphoma can be either classic Hodgkin’s disease or nodular lymphocytic predominant Hodgkin’s lymphoma — which is much rarer.

The main cause is not known but the disease has been linked to DNA mutations as well as to the Epstein-Barr Virus, which causes glandular fever.

Hodgkin’s disease most commonly affects people between the ages of 15 and 40 and people over 55.

The most common symptom of lymphoma is a painless swelling, often in the neck, armpit or groin. Other symptoms include fever, night sweats and weight loss.

It is considered one of the most treatable cancers, with more than 90 percent of patients surviving more than five years.

Treatment for Hodgkin’s lymphoma

How Hodgkin’s lymphoma is treated usually depends on what stage it is, but it is likely to be a combination of radiation therapy and chemotherapy.

In cases where chemotherapy and radiation are not sufficient in treating Hodgkin’s lymphoma, stem cell transplantation may be recommended.

This is only usually offered to patients who have relapsed Hodgkin’s disease. The idea behind having a stem cell transplant is replace and renew their bone marrow following intensive chemotherapy.

Commonly this will be autologous stem cell transplantation, which means a patient’s own non-cancerous stem cells are harvested prior to undergoing intensive chemotherapy and then re-injected into their bodies afterwards.

Allogeneic (from a donor) stem cell transplantation for Hodgkin’s lymphoma patients is also possible.

How might stem cell therapies help in the future?

Thymus

Chemotherapy and radiation therapy are known to not only deplete mature T-cells, but also to significantly damage the thymus, seen as the “university” of the immune system because it is where cells go to learn how to fight infection.

Recovering thymus function following a stem cell transplant can be delayed in some patients — and this delay is associated with a higher risk of infection and poor clinical outcome.

In rare cases, the thymus is affected by Hodgkin’s lymphoma. Because the thymus gland is so important to the body’s immune system scientists are exploring ways this gland can be grown for transplant or repaired using stem cells.

Experiments on mice have shown that when you take thymus progenitor cells (like stem cells, but more specific) and inject them into a mouse that is missing a thymus, the cells go on to make a fully functional thymus gland.

Single cell biology research

Although scientists have been examining cells under microscopes for 180 years the characteristics of individual cells remain elusive.

Stem cells may have very diverse functions but do not necessarily look obviously different to other cells.

A study published in Cell Stem Cell reveals the first time researchers have isolated single cells from populations of rare blood cells and used a technique to profile and test these stem cells’ capacity for transplantation.

The study, by Professor Bertie Göttgens and colleagues at the Cambridge University Department of Haematology, the Cambridge Institute for Medical Research and the Wellcome Trust/Medical Research Council Stem Cell Institute, brings with it the possibility of identifying the molecules that operate within a single stem cell and the potential outcomes for a transplant.

Although the exact implications for the treatment of cancers like Hodgkin’s and Non-Hodgkin’s lymphoma and leukaemia are unclear, the hope is that it will lead to the refinement of stem cell transplants, with targeted individual cells chosen.

Another method of improving stem cell transplants, involves stopping haemopoietic stem cells from dying before or during transplantation.

A transplant can be stressful for HSCs and therefore many die before they are integrated properly into the patient’s bone marrow. This means that blood cell formation is delayed and can result in transplant failure. It can also be particularly problematic if there weren’t enough donor stem cells to start with.

Apoptosis is the process in which HSCs die. Apoptosis applies to all cells, not just stem cells. It is mediated by the BIM and BMF proteins. Therefore, it follows that inhibiting these proteins from being expressed may prevent or down-regulate apoptosis.

This method, detailed in The Journal of Experimental Medicine on 7th September 2017, was achieved successfully in mice.

However, it was found that the BIM and BMF protein-inhibited HSCs caused auto-immune diseases and lymphomas within the mice. Therefore the researchers concluded that it was necessary to only temporarily inhibit these proteins, which would achieve the desired effects, of improving HSC ‘fitness’, without causing any long-term side effects.

This study presents the possibility that patients with lymphomas such as Hodgkin’s lymphoma could be treated more effectively with fewer donor stem cells in the future.