Acute myeloid leukemia risk factors

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]

Overview

Risk Factors

A number of risk factors for developing acute myeloid leukemia have been identified, including:

Preleukemia

"Pre-leukemic" blood disorders such as myelodysplastic or myeloproliferative syndromes can evolve into AML; the exact risk depends on the type of MDS/MPS[1]. Other hematological disorders that can progress to acute myeloid leukemia include:

Chemical exposure

Exposure to anti-cancer chemotherapy, in particular alkylating agents, can increase the risk for the subsequent development of acute myeloid leukemia. The risk is highest about 3–5 years after chemotherapy.[2] Other chemotherapy agents, specifically epipodophyllotoxins and anthracyclines, have also been associated with treatment-related leukemia. These treatment-related leukemias are often associated with specific chromosomal abnormalities in the leukemic cells.[3]

  • Ionizing radiation exposure can increase the risk of acute myeloid leukemia. Survivors of the atomic bombings of Hiroshima and Nagasaki had an increased rate of acute myeloid leukemia,[4] as did radiologists exposed to high levels of X-rays prior to the adoption of modern radiation safety practices.[5]
  • Occupational chemical exposure to benzene and other aromatic organic solvents is controversial as a cause of acute myeloid leukemia. Benzene and many of its derivatives are known to be carcinogenic in vitro. It is known to cause aplastic anemia and pancytopenia. While some studies have suggested a link between occupational exposure to benzene and increased risk of acute myeloid leukemia (M6 type),[6] others have suggested that the attributable risk, if any, is slight.[7]

Genetics

A hereditary risk for acute myeloid leukemia appears to exist. Multiple cases of acute myeloid leukemia developing in a family at a rate higher than predicted by chance alone have been reported.[8][9][10][11] Several congenital conditions may increase the risk of leukemia; the most common is probably Down syndrome, which is associated with a 10 to 18-fold increase in the risk of acute myeloid leukemia.[12] Other congenital disorders with such predisposition include:

References

  1. Sanz G, Sanz M, Vallespí T, Cañizo M, Torrabadella M, García S, Irriguible D, San Miguel J (1989). "Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: a multivariate analysis of prognostic factors in 370 patients". Blood. 74 (1): 395–408. PMID 2752119.
  2. Le Beau M, Albain K, Larson R, Vardiman J, Davis E, Blough R, Golomb H, Rowley J (1986). "Clinical and cytogenetic correlations in 63 patients with therapy-related myelodysplastic syndromes and acute nonlymphocytic leukemia: further evidence for characteristic abnormalities of chromosomes no. 5 and 7". J Clin Oncol. 4 (3): 325–45. PMID 3950675.
  3. Thirman M, Gill H, Burnett R, Mbangkollo D, McCabe N, Kobayashi H, Ziemin-van der Poel S, Kaneko Y, Morgan R, Sandberg A (1993). "Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations". N Engl J Med. 329 (13): 909–14. PMID 8361504.
  4. Bizzozero O, Johnson K, Ciocco A (1966). "Radiation-related leukemia in Hiroshima and Nagasaki, 1946–1964. I. Distribution, incidence and appearance time". N Engl J Med. 274 (20): 1095–101. PMID 5932020.
  5. Yoshinaga S, Mabuchi K, Sigurdson A, Doody M, Ron E (2004). "Cancer risks among radiologists and radiologic technologists: review of epidemiologic studies". Radiology. 233 (2): 313–21. PMID 15375227.
  6. Austin H, Delzell E, Cole P (1988). "Benzene and leukemia. A review of the literature and a risk assessment". Am J Epidemiol. 127 (3): 419–39. PMID 3277397.
  7. Linet, MS. The Leukemias: Epidemiologic Aspects. Oxford University Press, New York 1985.
  8. Taylor GM, Birch JM (1996). "The hereditary basis of human leukemia". In Henderson ES, Lister TA, Greaves MF. Leukemia (6th ed.). Philadelphia: WB Saunders. p. 210. ISBN 0-7216-5381-2.
  9. Horwitz M, Goode EL, Jarvik GP (1996). "Anticipation in familial leukemia". Am. J. Hum. Genet. 59 (5): 990–8. PMC 1914843. PMID 8900225.
  10. Crittenden LB (1961). "An interpretation of familial aggregation based on multiple genetic and environmental factors". Ann. N. Y. Acad. Sci. 91 (3): 769–80. Bibcode:1961NYASA..91..769C. doi:10.1111/j.1749-6632.1961.tb31106.x. PMID 13696504.
  11. Horwitz M (1997). "The genetics of familial leukemia". Leukemia. 11 (8): 1347–59. doi:10.1038/sj.leu.2400707. PMID 9264391.
  12. Evans D, Steward J (1972). "Down's syndrome and leukaemia". Lancet. 2 (7790): 1322. PMID 4117858.

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