Although chromosomal aberrations are the hallmark of ALL, they are not sufficient to generate leukemia. Genetic changes are usually linked to the overexpression or underexpression of various genes that regulate proliferation or maturation. Interestingly, a Philadelphia Chromosome (seen in CML) can be found in some ALL cases. This involves the BCR/ABL1 genes and the tyrosine kinases targeted by some CML treatments.
Some commonly seen genetic changes include:
- ETV6-RUNX1 (caused by a translocation of 12;21)
- IKZF1 (involves a deletion of a critical transcription factor important in B cell development)
- BCR/ABL1 (involves a kinase activating factor)
Predisposing factors that can lead to these changes include certain diseases such as Down Syndrome or Fanconi anemia, exposure to radiation, pesticides, or other biological or chemical toxins. However, most cases of ALL appear de novo in previously healthy individuals.
