Many types of gene mutations and chromosomal abnormalities are found in acute leukemia. As we will discuss later, these are, in fact, the basis of classification, treatment, and prognosis.
Typically, it is not just one gene that is mutated; multiple genetic changes must occur to cause the leukemia. We describe the genes affected as:
- Oncogenes. These can cause neoplastic conditions in various ways, such as changing how procarcinogens are metabolized, disabling the person's ability to repair DNA damage, altering the person's immune system, or affecting the regulation of cell growth.
- Protooncogenes. These genes are the upregulators of cell growth and when mutated, can become oncogenes.
- Tumor suppressor genes. These genes downregulate cell growth and, if altered, can result in unchecked proliferation.
The common chromosomal abnormalities seen in acute leukemia that can be visualized on chromosomal analysis include:
- Translocations. A piece of one chromosome can break off and attach to another chromosome. This is one of the most frequently seen chromosomal abnormalities in acute leukemia. The first translocation that was identified, however, was in Chronic Myeloid Leukemia—the famous Philadelphia Chromosome (later, this same translocation was found in other leukemias). Translocations can cause altered gene expression. For instance, they can position a promoter gene to turn on a cell cycle and replication gene.
- Inversions. This occurs when part of the chromosome is turned around, causing altered gene expression as well.
- Deletions. In a deletion, part of the chromosome breaks off and is lost. If the lost gene(s) are tumor suppressor genes, replication can continue unchecked.
- Additions. In this abnormality, part of a chromosome or an additional chromosome is gained. This can cause problems if several oncogenes are added.
