Acute Promyelocytic Leukemia (APML) is caused by a genetic mutation involving the PML gene on chromosome 15 and the RARA gene on chromosome 17.
The Genetic Basis of APML
The underlying cause of APML is a chromosomal translocation, specifically t(15;17). This means that a segment of chromosome 15 breaks off and attaches to chromosome 17, while a segment of chromosome 17 breaks off and attaches to chromosome 15.
Translocation t(15;17)
This translocation results in the fusion of:
- Part of the PML (Promyelocytic Leukemia) gene located on chromosome 15.
- Part of the RARA (Retinoic Acid Receptor Alpha) gene located on chromosome 17.
Resulting Fusion Gene: PML-RARA
The fusion of these genes creates a new, abnormal gene called PML-RARA. This PML-RARA gene produces an abnormal protein that disrupts normal blood cell development, particularly the maturation of promyelocytes (a type of immature white blood cell). This leads to an accumulation of these abnormal promyelocytes in the bone marrow, crowding out healthy blood cells and leading to the symptoms of APML.
Mechanism of Action
The PML-RARA protein interferes with the normal function of the retinoic acid receptor, which is crucial for cell differentiation. By blocking this differentiation process, the promyelocytes remain immature and proliferate uncontrollably.
In summary, APML is specifically caused by the t(15;17) translocation, which results in the PML-RARA fusion gene, leading to the abnormal development of promyelocytes.
