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Cell Signaling and CML
Transcript of Cell Signaling and CML
When you have too many white blood cells, they take up more room in the bone marrow than normal. So there is not enough space for making red blood cells and platelets. Red blood cells carry oxygen round the body. If there are not have enough of these, the person will be tired and breathless.
Platelets are vital for normal blood clotting. If you have too few platelets, you will have bleeding problems such as nosebleeds or a fine rash of red spots caused by bleeding into the skin. How people develop the disease Although researchers know what genes are involved in the development of CML, they do not yet know why some people get it and others do not. Some causes may be: Radiation
Radiation can increase risk to some extent because atomic bomb survivors had an increased risk of leukemia. Use of radiotherapy for another cancer in the past could increase your risk of developing CML. But the risk is very small, compared to the benefit of the radiotherapy in treating the cancer. Low immunity
An analysis of published studies has shown that people with low immunity due to HIV or AIDS are 3 times more likely to develop leukemia than the general population. People who take drugs that lower their immunity after an organ transplant are twice as likely to develop leukemia. Ulcerative colitisOne study showed that people with the inflammatory bowel condition, ulcerative colitis, have almost double the risk of myeloid leukemia compared to the general population. Using pesticides at workA review looked at published evidence for men exposed to pesticides as part of their work (for example, farmers or agricultural workers). The review showed that the men had a 40% increase in their CML risk compared to the general population. BenzeneContact with a type of chemical called benzene for some years may increase CML risk. Benzene is one of the chemicals in petrol. It is also a solvent used in the rubber industry. Body weight
A combined review of 4 previously published studies showed that the risk of CML is increased by about a quarter for people who are overweight or obese, compared to people with a healthy body weight. Cell Signaling and CML The fusion protein BCR/ABL produced by the Philadelphia chromosome activates continuesly the cytosolic tyrosine kinase ABL that normally would be activated only when the cell is stimulated by a growth factor. The result: chronic myelogenous leukemia.
It is a receptor tyrosine kinases pathway. A, BCR-ABL signaling pathways activated in CML. Dimerization of BCR-ABL triggers autophosphorylation events that activate the kinase and generate docking sites for intermediary adapter proteins such as GRB2. BCR-ABL–dependent signaling facilitates activation of multiple downstream pathways that enforce enhanced survival, inhibition of apoptosis, and perturbation of cell adhesion and migration. Symptoms Chronic myelogenous leukemia is grouped into several phases:
The chronic phase can last for months or years. The disease may have few or no symptoms during this time. Most people are diagnosed during this stage, when they are having blood tests done for other reasons.
The accelerated phase is a more dangerous phse. Leukemia cells grow more quickly. Common symptoms include fever (without infection), bone pain, and a swollen spleen.
Blast Crisis: some symptoms may include
Infection due to bone marrow failure
Excessive sweating (night sweats)
Pressure under the lower left ribs from a swollen spleen
Rash - small pinpoint red marks on the skin
Weakness Treatments Drugs and Medicines •Dasatinib (Sprycel) and nilotinib (Tasigna): Dasatinib and nilotinib are two additional FDA-approved drugs that, like imatinib, are taken in pill form and treat CML by blocking the gene that causes cells to grow and divide. Both drugs, especially nilotinib, have been shown to be more effective than imatinib for some patients when used as initial therapy.
•Ponatinib: A new drug called ponatinib may soon be approved by the FDA. Ponatinib has shown promise for patients whose CML has relapsed or progressed, or who cannot tolerate treatments that are currently approved. •Gleevec: Imatinib mesylate, taken as a daily pill, has been the standard treatment for people newly diagnosed with CML. The first in a series of ‘targeted’ therapies for CML, imatinib works by shutting down the protein that causes CML cells to grow and divide. In eight out of 10 patients treated with imatinib, the Ph chromosome disappears completely. Gleevec is an inhibitor of specific tyrosine kinases that targets platelet-derived growth factor (PDGF) receptor.The kinase in effect prevents the formation of a product formed by the fusion of PDGF and Philadelphia (Ph) chromosome (expressed in CML). Stem cell transplantation is the only treatment that provides a potential cure for CML. A patient receives high doses of chemotherapy to destroy the bone marrow along with the leukemia cells in the body, and suppress the immune system. This is followed by an infusion of healthy, blood-forming stem cells donated by another person who has a nearly identical tissue type (either a family member or an unrelated donor). Chemotherapy may also be used to stop or slow the growth of cancer cells before stem cell transplantation. Targeted therapy uses drugs to identify and attack the cancer cells without hurting the normal cells. These drugs, called tyrosine kinase inhibitors, target the cancer cells in CML and may be used as the first treatment for patients with an early phase CML. Bone marrow transplant can be an option for some people whose CML advances or if multiple medicines have failed. To be eligible for a transplant, you need a well-matched donor—ideally a close relative like a brother or sister. Talk with your doctor about the potential benefits and risks of this treatment. Because the risks associated with bone marrow transplants increase with age, this procedure is usually recommended only for younger patients who have already tried various other treatments. Biological therapies harness your body's immune system to help fight cancer. The biological drug interferon is a synthetic version of an immune system cell. Interferon may help reduce the growth of leukemia cells. Interferon may be an option if other treatments don't work or if you can't take other drugs, such as during pregnancy. Side effects of interferon include fatigue, fever, flu-like symptoms and weight loss.