Chronic myelogenous leukemia causes
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Overview
Chronic myelogenous leukemia is caused by an abnormal chromosome develops, the abnormal chromosome creates a new gene which amplifies the production rate of cells derived from hematopoeitic stem cells. First, an abnormal chromosome develops. In people with chronic myelogenous leukemia, the Philadelphia chromosome, named for the city where it was discovered, is present in the blood cells of >95 percent of people. Second, the abnormal chromosome creates a new gene, the Philadelphia chromosome creates a new gene called BCR-ABL. It contains instructions that tell the abnormal blood cell to produce too much of a protein called tyrosine kinase that promotes cancer by allowing certain blood cells to grow out of control.
Causes
Chronic myelogenous leukemia is caused by:[1]
- First, an abnormal chromosome develops.
- In people with chronic myelogenous leukemia, the Philadelphia chromosome, is present in the blood cells of > 95% of people.[2]
- Second, the abnormal chromosome creates a new gene.
- The Philadelphia chromosome creates a new gene called BCR/ABL. It contains instructions that tell the abnormal blood cell to produce too much of a protein called tyrosine kinase that promotes cancer by allowing certain blood cells to grow out of control.[3]
- Third, the new gene allows too many immature blood cells.
- In chronic myelogenous leukemia, this process doesn't work correctly and the tyrosine kinase caused by the BCR/ABL gene causes too many white blood cells. These diseased white blood cells build up in huge numbers, crowding out healthy blood cells and damaging the bone marrow.[4]
- Fourth, In a very small number of CML patients, the leukemia cells have the BCR/ABL oncogene but not the Philadelphia chromosome.
- In an even smaller number of people who seem to have CML, neither the Philadelphia chromosome nor the BCR-ABL oncogene can be found. They might have other, unknown oncogenes causing their disease.[5]
- Other causes include, sometimes people inherit DNA mutations from a parent that greatly increase their risk of getting certain types of cancer. But mutations passed on by parents do not cause CML.[6][7]
- DNA changes related to CML occur during the person's lifetime, rather than having been inherited before birth.[8]
References
- ↑ "Chronic myelogenous leukemia - Symptoms and causes - Mayo Clinic".
- ↑ Zahra K, Ben Fredj W, Ben Youssef Y, Zaghouani H, Chebchoub I, Zaier M, Badreddine S, Braham N, Sennana H, Khelif A (2012). "Chronic myeloid leukemia as a secondary malignancy after lymphoma in a child. A case report and review of the literature". Onkologie. 35 (11): 690–3. doi:10.1159/000343952. PMID 23147546.
- ↑ Van Etten RA (August 2003). "c-Abl regulation: a tail of two lipids". Curr. Biol. 13 (15): R608–10. PMID 12906815.
- ↑ Konopka JB, Witte ON (November 1985). "Detection of c-abl tyrosine kinase activity in vitro permits direct comparison of normal and altered abl gene products". Mol. Cell. Biol. 5 (11): 3116–23. PMC 369126. PMID 3879812.
- ↑ Giles FJ, Cortes J, Jones D, Bergstrom D, Kantarjian H, Freedman SJ (January 2007). "MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation". Blood. 109 (2): 500–2. doi:10.1182/blood-2006-05-025049. PMID 16990603.
- ↑ Howlader N, Noone AM, Krapcho M, et al (eds). SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations), National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2009_pops09/, based on November 2011 SEER data submission, posted to the SEER web site, April 2012
- ↑ Druker BJ, Marin D. Chronic myelogenous leukemia. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita. Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2015:1644-1653.
- ↑ Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, Moiraghi B, Shen Z, Mayer J, Pasquini R, Nakamae H, Huguet F, Boqué C, Chuah C, Bleickardt E, Bradley-Garelik MB, Zhu C, Szatrowski T, Shapiro D, Baccarani M (June 2010). "Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia". N. Engl. J. Med. 362 (24): 2260–70. doi:10.1056/NEJMoa1002315. PMID 20525995.