2.1. Acute promyelocytic leukemia

Gene mutations can be acquired during a person's lifetime and are present only in certain cells. These mutations are called somatic mutations, and they are not inherited. A somatic mutation involving the PML gene causes acute promyelocytic leukemia, a cancer of the blood forming tissue (bone marrow). Acute promyelocytic leukemia is characterized by an accumulation of immature white blood cells, called promyelocytes, in the bone marrow. A rearrangement (translocation) of genetic material between chromosomes 15 and 17, written as t(15;17), fuses part of the PML gene on chromosome 15 with part of another gene on chromosome 17 called RARA. The protein produced from this fused gene, PML-RARα, functions differently than the protein products of the normal PML and RARA genes.

The PML-RARα protein does not localize to the PML-NBs, and the structures do not form properly. The PML-RARα protein is unable to block cell proliferation or induce apoptosis.

Additionally, the function of the RARα protein, the product of the RARA gene, is disrupted. Normally, this protein is involved in the regulation of gene transcription, which is the first step in protein production. Specifically, this protein helps control the transcription of certain genes important in the maturation (differentiation) of white blood cells beyond the promyelocyte stage. However, the PML-RARα protein blocks (represses) gene transcription.

The PML-RARα protein allows abnormal cell proliferation and blocks the differentiation of white blood cells at the promyelocyte stage. As a result, excess promyelocytes accumulate in the bone marrow and normal white blood cells cannot form, leading to acute promyelocytic leukemia.