Leukemia is a malignant disease (cancer) that originates in a cell in the marrow. It is characterized by the uncontrolled growth of developing marrow cells. There are two major classifications of leukemia: myelogenous or lymphocytic, which can each be acute or chronic. The terms myelogenous or lymphocytic denote the cell type involved. Thus, four major types of leukemia are: acute or chronic myelogenous leukemia and acute or chronic lymphocytic leukemia.
Acute leukemia is a rapidly progressing disease that results in the accumulation of immature, functionless cells in the marrow and blood. The marrow often can no longer produce enough normal red and white blood cells and platelets. The lack of normal white cells impairs the body's ability to fight infections. A shortage of platelets results in bruising and easy bleeding. Chronic leukemia progresses more slowly and permits greater numbers of more mature, functional cells to be made. New Cases Among an estimated 31,500 new cases of leukemia in the United States this year, about equal proportions are acute leukemia and chronic types. Most cases occur in older adults; more than half of all cases occur after age 60. Leukemia usually strikes ten times as many adults as children. Leukemia is the most common cancer among children and acute lymphocytic leukemia (ALL) accounts for 80 percent of the childhood leukemia cases.
Acute myeloid leukemia, which is very often fatal and is the form of cancer found to be most increased among flight crews [The Lancet, December 23, 2000; p.356], has an average survival time of 3 to 4 years following diagnosis.
Myeloid leukemia usually strikes men in their 30s and 40s. Even in patients who experience complete remission, recurrence is common. The disease develops rapidly, with symptoms including anemia, fever, bleeding, and swelling of the lymph nodes. Immature leukemia cells continue to divide in the bone marrow, which leads to rapid death if left untreated. It affects granulocytes and monocytes, white blood cells that destroy bacteria and some parasites.
Growth, pro-inflammatory, and immuno-suppressive cytokines often expressed by leukemias and lymphomas are:
Vascular endothelial growth factor (VEGF). VEGF is considered essential for cancer cell survival and angiogenesis (the formation of new blood vessels). High levels of VEGF correlate with shortened survival in chronic lymphocytic leukemia (Ferrajoli et al. 2001).
Basic fibroblast growth factor (bFGF). bFGF is a potent mitogen (growth signal) and is essential for angiogenesis. Simultaneous elevations in bFGF and VEGF are an independent predictor of a poor prognosis in non-Hodgkin's lymphoma (Salven et al. 2000).
Hepatocyte growth factor (HGF). Also known as a multiple function factor, HGF protects cancer cells from cytotoxic agents, contributes to the development of chemo-resistance, and stimulates hematopoiesis (Skibinski et al. 2001). (Hematopoiesis refers to the formation and development of blood cells occurring primarily in the bone marrow and to a lesser extent the lymph nodes.)
Epidermal growth factor (EGF). EGF is essential to the hyper-proliferation of some lymphomas and to epidermal cells (Courville et al. 1999).
Tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is a pro-inflammatory cytokine significantly elevated in all leukemias except for AML and myelodysplastic syndromes (Aguayo et al. 2000).
Interleukin-6 (IL-6). IL-6 is a pro-inflammatory and immunosuppressive cytokine. Elevations in serum IL-6 correlate with adverse disease features and shortened survival in chronic lymphocytic leukemia (Fayad et al. 2001).
The lymphomas and leukemias that can overexpress these cytokines are:
- Hodgkin's disease - VEGF, bFGF, HGF
- T-cell lymphoma - VEGF, EGF
- Non-Hodgkin's lymphoma - VEGF, bFGF, HGF, TNF-alpha, IL-6
- Burkitt's lymphoma - HGF, EGF
- Chronic myeloid leukemia - VEGF, bFGF, HGF, TNF-alpha, IL-6
- Acute myeloid leukemia - VEGF, bFGF, HGF
- Chronic myelomonocytic leukemia - VEGF, bFGF, HGF, TNF-alpha
- Acute lymphoblastic leukemia - bFGF, HGF, TNF-alpha
- Chronic lymphocytic leukemia - VEGF, bFGF, HGF, TNF alpha, IL-6
- Myelodysplastic syndromes - VEGF, bFGF, HGF