Acute Myeloid Leukemia: Causes

Pathogenesis (disease development)

In acute myeloid leukemia, there is mass shedding of immature blasts (young, not finally differentiated cells) into the peripheral blood. The precursor of secondary acute myeloid leukemia (sAML) is myelodysplastic syndrome (MDS) in approximately one-third of cases. MDS and sAML are highly clonal cancers. In 18% of AML patients, a DNMT3A mutation is detectable (premalignant stem cell). This remains detectable even in patients who have been cured long-term.

Etiology (Causes)

Biographic causes

  • Genetic burden from parents, grandparents
    • Genetic diseases
      • Ataxia teleangiectatica (synonyms: ataxia teleangiectasia; Louis-Bar syndrome; Boder-Sedgwick syndrome) – genetic disorder with autosomal recessive inheritance that leads to ataxia (gait disturbances), short stature, and high susceptibility to infection, among other symptoms.
      • Bloom syndrome (synonym: congenital teleangiectatic syndrome) – rare, genetic disease with autosomal recessive inheritance, which can lead, among other things, to short stature and various malignant (malignant) diseases (eg leukemia).
      • Fanconi anemia [in 50-60% of AML chromosomal aberrations are found, which are usually of considerable prognostic relevance;/ see also WHO classification) – genetic disease with autosomal recessive inheritance, which occurs in childhood and can lead to hematological neoplasia (malignant neoplasm of hematopoietic cells); typical sign of Fanconi anemia is, among others. a. the regression of the bone marrow (severe aplastic anemia) – a pancytopenia (synonym: tricytopenia; reduction of all three cell series in the blood) is common in this case.
      • Kostmann syndrome (synonym: Kostmann disease, severe congenital neutropenia) – rare genetic disease with autosomal dominant inheritance, in which from birth in the blood too few or no neutrophil granulocytes (immune defense cells,which belong to the white blood cells) to be found (agranulocytosis).
      • Trisomy 21 (Down syndrome) – special genomic mutation in humans in which the entire 21st chromosome or parts of it are present in triplicate (trisomy) (occurrence usually sporadic). In addition to physical characteristics considered typical for this syndrome, the cognitive abilities of the affected person are usually impaired; furthermore, there is an increased risk of leukemia.

Behavioral causes

Disease-related causes

Drugs

  • Azathioprine
  • Previous chemotherapy
    • Especially with alkylanzines (onset of leukemia 4-6 years after application and aberrations on chromosomes 5 and/or 7) and topoisomerase II inhibitors (anthracyclines, anthraquinones, epipodophylotoxins) with leukemia onset 1-3 years after exposure.
    • Solid tumors (highest risk: bone cancer (SIR 39.0; 95% confidence interval 21.4-65.5), soft tissue cancer (SIR 10.4; 6.4-15.9), and testicular cancer (SIR, 12.3; 7.6-18.8); tumors in peritoneum, lungs (small cell carcinoma), ovary, fallopian tubes, or central nervous system: SIR 5- to 9-fold; other cancers: SIR 1.5 to 4 times).

Environmental pollution – intoxications (poisonings).

  • Radiation exposure (ionizing radiation), especially in combination with the administration of alkylanzien and etoposide (cytostatics).
  • Benzene
  • Exposure to petroleum products, paints, ethylene oxides.
  • Formaldehyde
  • Herbicides (weed killers)
  • Pesticides (pesticides)