What causes acute lymphoblastic leukemia (ALL)?

Updated: Jun 20, 2019
  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

A review of the genetics, cell biology, immunology, and epidemiology of childhood leukemia by Greaves concluded that B-cell precursor ALL has a multifactorial etiology, with a two-step process of genetic mutation and exposure to infection playing a prominent role. The first step occurs in utero, when fusion gene formation or hyperdiploidy generates a covert, pre-leukemic clone. The second step is the postnatal acquisition of secondary genetic changes that drive conversion to overt leukemia. Only 1% of children born with a pre-leukemic clone progress to leukemia. [1, 2]

The second step is triggered by infection. Triggering is more likely to occur in children whose immune response is abnormally regulated because they were not exposed to infections in the first few weeks and months of life. Lack of exposure to these early infections, which prime the immune system, is more likely to occur in societies that are zealous about hygiene; this would help explain why at present, pediatric ALL is seen primarily in industrialized societies. [1, 2]

Less is known about the etiology of acute lymphoblastic leukemia (ALL) in adults compared with acute myeloid leukemia (AML). Most adults with ALL have no identifiable risk factors.

Although most leukemias occurring after exposure to radiation are AML rather than ALL, an increased prevalence of ALL was noted in survivors of the Hiroshima atomic bomb but not in those who survived the Nagasaki atomic bomb.

A analysis of the Surveillance, Epidemiology and End Results (SEER) database showed that the incidence of ALL was higher than expected in patients with a prior history of Hodgkin lymphoma, small cell lung cancer, and ovarian cancer. [3]


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