Treating Lymphoma and Leukemia with Hematopoietic Stem Cells


By: Madison Altendorf
May 17, 2011
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Human Stem Cell


Abstract



This research of Hematopoietic Stem Cells will provide basic information about what these stem cells are, their important role inside the human body, the medical uses that HSCs provide that can help cure diseases, specifically lymphoma and leukemia and the controversies that surround the use of embryonic stem cells. The studies of HSCs are just the beginning of very important and groundbreaking research that could someday lead to the treatment of cancer and other diseases such as lupus, multiple sclerosis and Parkinson's.


Introduction



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Embryonic Stem Cells

What is a stem cell?

Stem Cells are the building blocks of the human body. They are "the most basic cell of the human body and develop into the approximately 250 different types of sophisticated cells that constitute the human body"(De Trizio, E, & Brennan, C. (2004). There are three different types of stem cells. Embryonic stem cells originate from disaggregated preimplantation embryos and are "pluripotent" meaning they have unlimited potential in their ability to differentiate. "These stem cells are found in the inner cell mass of human embryos that have achieved the blastocyst stage of development, which occurs three to five days after fertilization of the human egg"(De Trizio, E, & Brennan, C. (2004). The second type are embryo germ cell stem cells (EG cells) derived from aborted fetuses. The third type are Adult Stem Cells which derive from mature tissue in the body. These stem cells are limited in their ability to differentiate but are less controversial to use in medical treatment. Stem cells can develop into many different cell types in the body and serve as the starting foundation in a human fetus. Stem cells have the ability of transforming into liver, kidney or heart cells. This ability of differentiation allows stem cells to perform specific functions to create a human being. Another property stem cells possess is the ability to repair any damaged cells in the body. A stem cell can divide and become specialized. It can become a muscle cell if the body needs it or can it can become a hematopoietic stem cell.

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Chart 1: Differentiation of a HSC

What is a Hematopoietic Stem Cell and why do we care about them?

Hematopoietic stem cells are stem cells that originate in bone marrow and can also be found in umbilical cord blood of a fetus, in an embryo or in peripheral blood in the human body. They are specialized cells that can become many different types of blood cells such as erythrocytes, basophils, neutrophils and B-lymphocytes (see chart 1 for more indepth detail on what HSCs can differentiate into). Hematopoietic stem cells can also undergo apoptosis, programmed cell death, which alerts the stem cells to stop proliferating when they are unneeded and causes them to self destruct. HSCs (Hematopoietic Stem Cells) are extremely important little cells to have, especially when a patient has a disease such as lymphoma and leukemia. Although using HSCs as treatment is controversial, HSCs have provided an important service when it comes to treating lymphoma and leukemia (5. Hematopoietic Stem Cells. In Stem Cell Information [World Wide Web site]. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, 2011)


Why research stem cells?

Stem cell research is a fascinating subject that I find very interesting. The ability for a cell to differentiate itself into any cell for the body to use and repair itself is remarkable. It also offers so many treatment options that is very exciting for future treatment of diseases. Imagine a world with no leukemia, lymphomas, HIV, multiple sclerosis or lupus. The possibilities of usage for HSCs are endless and it is just a matter of time before the are fully utilized in everyday medicine.


Discussion


What is Lymphoma and Leukemia?

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Picture of Bone Marrow where Leukemia begins. (Acute myeloid leukemia needs proper care and guidence, 2010).

Leukemia:


Leukemia and lymphoma are two types of cancer where HSCs can aid in their treatments. Leukemia is cancer of the blood cells that starts in bone marrow, the soft tissue inside most bones. In a patient with Leukemia, the bone marrow begins to make abnormal white blood cells that grow at a rapid rate and dont stop. Overtime, these white blood cells can crowd the normal blood cells and lead to medical problems such as anemia and
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Reed-Sternberg cells are common in classic Hodgkin Lymphoma. They are abnormal lymphocytes that may contain more than one nucleus. (University of Minnesota, 2010).

infections. Leukemia can either be acute or chronic. Acute Leukemia happens very fast and the patient gets sick quickly where chronic leukemia gets worse slowly and a patient might not know they have it for many years due to a lack of symptoms. Leukemia can also be either lymphocytic or myelogenous. Lymphocytic leukemia affects white blood cells called lymphocytes where myelogenous leukemia affects another type of white blood cells called myelocytes (Leukemia-topic overview. (2008, November 26).

Lymphoma:


Lymphoma refers to cancer of the lymphatic system. Lymphoma starts in the lymphocytes and rapidly grows to produce cancer cells that attack the body. There are two main types of lymphoma. Hodgkin's lymphoma and non-Hodgkin's lymphoma. These two types of lymphoma occur in the same place of the body, have the same symptoms but look differently upon examination under a microscope (Balentine, J. (2011)." In Hodgkin's disease, cells in the lymphatic tissues grow in a rapid and uncontrolled manner-the defining characteristic of cancer. If not treated in time, the cancer may spread to other organs, such as the lungs, liver and bone marrow. In addition, the proliferation of abnormal lymphocytes reduces the number of healthy lymphocytes. The resulting impairment of the immune system leaves the body susceptible to serious infection" John Hopkins Medicine, . (2008).



Hematopoietic Stem Cells and Cancer Treatments


Both leukemia and lymphoma must be treated in order for the patient to survive and there are a few options that a patient can consider for treatment.
  1. Chemotherapy: Chemotherapy, or more commonly known as "chemo", is a treatment for cancer that uses strong drugs to stop cancer cells from growing and spreading. Patients who choose chemo as their cancer treatment method have a regimen that they must stick to in order for the drugs to be effective. The chemo works to kill cancer cells, but unfortunatly will kill other fast growing cells in the body, not being able to distinguish between healthy and diseased cells. The most commonly affected cells in the body are hair and blood cells, two types of cells that rapidly multiply. This can lead to a serious condition known as neutropenia, where the body doesn't have enough white blood cells to fight off infections.
  2. Radiation: Radiation is another treatment that a cancer patient can choose to undergo. The technique requires a machine used outside the body that delivers high-energy radiation to shrink tumor or cancer cells. This process damages the cell's DNA or creates charged particles called "free radicals" within the cell that can, in-turn, damage its DNA. Radiation, like chemo, does not just kill cancer cells in the body but can damage normal cells as well. Doctors will try to map out a radiation plan so that the least amount of healthy cells will be affects.

In both of these treatment options, healthy cells of the body will be damaged or destroyed. This is where Hematopoietic stem cells come into play. A patient will be placed on low to medium levels of chemo or radiation so as not to damage too many healthy cells. This leve of precaution that must be taken, might not be able to get rid of all the cancer. Increasing radiation/chemo levels can be very detrimental to the patient's health and they might not be able to recover from the lack of so many vital cells. If HSCs were transplanted into a patient after an intensive cancer treatment, their ability to recover would increase and because their treatments were intensified, hopefully all the cancer will be treated and the patient will be in remission.


HSC Transplantation
After cancer patients have undergone treatment, either radiation or chemotherapy, they can then have HSCs transplanted. HSCs are transplanted either by a bone marrow transplant or with a transplant of HSCs collected from the peripheral circulation of a matched donor. Normally a donor would be a close relative

who has similar human leukocyte antigens. There is the chance that sometimes a donor's HSCs and the patient receiving them will be rejected. "The goal of bone marrow transplants is to enable the recipient to produce healthy red blood, or immune system, cells. However, such transplants can result in graft-versus-host (GVH) disease. The transplanted bone marrow contains immunocompetent cells that mount primarily a cell-mediated immune response against the tissue into which they have been transplanted. Because the recipient lack effective immunity, GVH disease is a serious complication and can even be fatal." (Tortorta, Gerard J., Berdell R. Funke, and Christine L. Case, 2010).For a less risky approach, a patient can donate their own stem cells to be harvested and stored. Once they are finished with their treatment, their own cells can be transplanted back into their body. There is no risk of rejection since the HSCs belong to them, but the patient runs the risk of cancerous cells being accidentally harvested and transplanted back into the body. "A team of investigators finds that they can prevent reintroducing cancer cells by purifying the cells and preserving only the cells that are CD34+, Thy-1+" (Negrin, R.S., Atkinson, K., Leemhuis, T., Hanania, E., Juttner, C., Tierney, K., Hu, W.W., Johnston, L.J., Shizurn, J.A., Stockerl-Goldstein, K.E., Blume, K.G., Weissman, I.L., Bower, S., Baynes, R., Dansey, R., Karanes, C., Peters, W., and Klein, J. (2000).)


Bone Marrow Transplant Video Mayo Clinic, (2009)

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("Stem cell research controversey," 2010)

Criticisms around using HSCs.
Why would our society not want to utilize a scientific tool that can have the potential to cure diseases? One would think that using stem cells as treatment would be the obvious choice. But many people including the Catholic Church feel that obtaining stem cells from recently aborted fetuses or "spare embryos" is wrong or evil. Using embryonic stem cells or embryonic germ cells raises the moral question for those who think that abortion or destroying a perfectly healthy embryo is morally wrong (Chapman, A, Ph.D, Frankel, M, Ph.D, & Garfinkel, M, Ph.D. (1999)). When an embryo is used to harvest embryonic stem cells, "that embryo no longer has the ability to develop through implantation in the human uterus. It is the termination of the embryo's viability to develop into a human being that has prompted fierce opposition around the world based on religious, moral and ethical considerations" (De Trizio, E, & Brennan, C. (2004)). Since the method of obtaining these types of stem cells is so controversial, the United States has not received much funding, and using this method of treatment is expensive and not used as common practice. Using Adult stem cells has proven to be much easier in-terms of extracting and
much less controversial since extracting HSCs can be done through a bone marrow extraction or taking the
patients blood and transplanting it back into their own body. The problem with using Adult HSCs is that they are not able to differentiate like an embryonic stem cell can thus making them not as useful as embryonic stem cells.


Literature Cited


  1. Acute myeloid leukemia needs proper care and guidence. (2010). [Web]. Retrieved from http://www.herbalgranny.com/2010/08/13/acute-myeloid-leukemia-needs-proper-care-and-guidance/(bone marrow pic)
  2. Balentine, J. (2011). Lymphoma. Retrieved from http://www.emedicinehealth.com/lymphoma/article_em.htm
  3. Chapman, A, Ph.D, Frankel, M, Ph.D, & Garfinkel, M, Ph.D. (1999). Stem cell research and applications. monitoring the frontiers of biomedical research. Retrieved from http://www.aaas.org/spp/sfrl/projects/stem/report.pdf
  4. De Trizio, E, & Brennan, C. (2004). The business of human embryonic stem cell research and an internal analysis of relevant laws. The Journal of Biolaw & Business, 7(4), Retrieved from http://www.dechert.com/library/BusinessOfStemCellResearch.pdf
  5. John Hopkins Medicine, . (2008). Lymphoma, hodgkin's disease. Retrieved from http://hopkins.portfolio.crushlovely.com/reference/article/lymphoma-hodgkins-hodgkins-disease
  6. Leukemia-topic overview. (2008, November 26). Retrieved from http://www.webmd.com/cancer/tc/leukemia-topic-overview
  7. Mayo Clinic, (2009). Bone Marrow Transplant [Web]. Available from http://www.youtube.com/watch?v=GIy2nMnuGGI (bone marrow transplant video)
  8. Negrin, R.S., Atkinson, K., Leemhuis, T., Hanania, E., Juttner, C., Tierney, K., Hu, W.W., Johnston, L.J., Shizurn, J.A., Stockerl-Goldstein, K.E., Blume, K.G., Weissman, I.L., Bower, S., Baynes, R., Dansey, R., Karanes, C., Peters, W., and Klein, J. (2000). Transplantation of highly purified CD34+Thy-1+hematopoietic stem cells in patients with metastatic breast cancer. Biol. Blood Marrow Transplant. 6, 262–271.–271.
  9. Stem cell research controversey [Web log message]. (2010, November 11). Retrieved from http://kennedysdisease.blogspot.com/2010/11/stem-cell-research-controversy.html
  10. Tortora, Gerard J., Berdell R. Funke, and Christine L. Case. Microbiology An Introduction. 10th ed. San Francisco: Pearson Prentice Hall, 2010. Print.
  11. University of Minnesota.(2010).Bone marrow biopsy. [Web]. Retrieved from http://www.cancer.umn.edu/cancerinfo/NCI/CDR257991.html (lymphocyte pic)
  12. 5. Hematopoietic Stem Cells. In Stem Cell Information [World Wide Web site]. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services,2011[cited Tuesday, May 17, 2011] Available at <http://stemcells.nih.gov/info/scireport/chapter5>