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Blood Cell Disorders

Blood Disorder Research at the McEwen Centre
Background: What are Blood Cell Disorders?
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Research in this field at the McEwen Centre focuses on understanding the biology of blood stem cells - both normal and malignant. Understanding how they differentiate and how things go wrong when cancer develops is an essential step towards the development of new therapies.

• Dr. John Dick was the first to discover that certain types of leukemia arise from a cell that shares the properties of a stem cell. These leukemia stem cells are thought to be responsible for propagation and progression of the disease. Dr. Dick’s research is aimed at studying the changes that turn normal stem and progenitor into cancerous cells as well as identifying new therapies to specifically target and destroy these cells.

• Dr. Norman Iscove is studying the genes and mechanisms involved in self-renewal and differentiation in normal and leukemic hematopoietic stem cells. In other words: when a blood stem cell divides, what are the factors determining whether it will make a copy of itself or become any one of the various types of cells present in the blood? One of Dr. Iscove’s research goals is to identify key genes responsible for the maintenance and extinction of human leukemia cells – such genes could be of therapeutic potential.

• Dr. Gordon Keller’s research team studies blood cell formation from both mouse and human embryonic stem cells. One of the objectives of this research program is to produce blood forming stem cells as well as other blood cell types from embryonic stem cells. This could potentially provide an unlimited disease-free supply of cells for transplantation.

• Dr. Andras Nagy’s team is investigating blood vessel development in normal and pathological conditions. Dr. Nagy’s interests also include the use of ES cells as a genetic model for the mouse and the study of self-renewal and early differentiation in embryonic stem cells.

• Dr. Peter Zandstra is studying how soluble factor communication networks between different blood cell types regulate blood stem cell growth and differentiation. His group is using information from these studies to develop systems for growing transplantable blood stem cells and to understand the feedback mechanisms that control stem cell number post transplantation.

Background: What are Blood Cell Disorders?

Disorders that affect blood cells or proteins in the blood systems are called blood disorders or hematological disorders. Blood disorders can result from changes in the number or effectiveness of specific blood cell types. Some examples of blood disorders include anemia (reduced red blood cell count), leukemia (increased white blood cell count specifically in the bone marrow), and sickle cell anemia (abnormally shaped red blood cells). Leukemia is the main focus of the Blood Disorders research group at the McEwen Centre for Regenerative Medicine.

Leukemia

Most mature blood cells have a short life span and therefore need to be constantly replaced throughout adult life. New blood cells are produced in the adult bone marrow from a specialized group of cells known as blood-forming or hematopoietic stem cells. The production of mature blood cells from these hematopoietic stem cells, a process known as hematopoiesis, occurs in a step-wise fashion involving the formation of intermediate populations known as progenitor cells. In leukemia, blood cell formation is altered and often blocked at the progenitor stage of development, resulting in the overgrowth of immature cells and a lack of production of specific types of mature cells. The excessive proliferation of these abnormal or malignant immature cells affects the normal production of blood cells and can result in a number of complications including problems with coagulation, increased susceptibility to infections and anemia.

Current Therapies for the Treatment of Leukemia

• Radiation Therapy
• Combining Chemotherapy with Bone Marrow or Stem Cell Transplant

High doses of chemotherapy can effectively destroy leukemic cells. However, this treatment also destroys the body’s normal blood forming system, including the stem cells. To overcome this problem, patients are given a bone marrow or stem cell transplant to rebuild a new blood forming system following the destruction of the leukemic population with chemotherapy. Bone marrow transplantation has been in use for over 30 years and is the most successful cell replacement therapy developed to date. This therapy highlights the power of regenerative medicine and the use of cell replacement strategies for treating disease.

More information on leukemia, blood disorders and current therapies:

• Canadian Cancer Society - Leukemia (CA)
• National Cancer Institute - Leukemia (US)
• The Leukemia and Lymphoma Society (US)
• Medline Plus – Blood Disorders
  a Service of the National Institutes of Health and the US Library of Science