Pathogenesis
Acute promyelocytic leukemia is characterized by a chromosomal translocation involving the retinoic acid receptor-alpha gene on chromosome 17 (RARα). In 95% of cases of APL, retinoic acid receptor-alpha (RARα) gene on chromosome 17 is involved in a reciprocal translocation with the promyelocytic leukemia gene (PML) on chromosome 15, a translocation denoted as t(15;17)(q24;q21). The RAR receptor is dependent on retinoic acid for regulation of transcription.
Four other gene rearrangements have been described in APL fusing RARα to promyelocytic leukemia zinc finger (PLZF), nucleophosmin (NPM), nuclear matrix associated (NUMA), or signal transducer and activator of transcription 5b (STAT5B) genes. All of these rearrangements are ATRA-sensitive, except for PLZF/RARα, which is resistant to ATRA.
The fusion of PML and RAR creates a hybrid protein with altered functions. This fusion protein binds with enhanced affinity to sites on the cell's DNA, blocking transcription and differentiation of granulocytes. It does so by enhancing interaction of nuclear co-repressor (NCOR) molecule and histone deacetylase (HDAC). Although the chromosomal translocation involving RARα is believed to be the initiating event, additional mutations are required for the development of leukemia.
APL most distinguishable trait is the presence of overt coagulopathy (disseminated intravascular coagulation) at diagnosis. The bleeding diathesis is due to the enhanced fibrinolytic activity due to annexin II overexpression and expression of tissue factor by abnormal promyelocytes.
The hypergranular form of APL features faggot cells. This term is applied to these blast cells because of the presence of numerous Auer rods in the cytoplasm. The accumulation of these Auer rods gives the appearance of a bundle of sticks, from which the cells derive their name.
Read more about this topic: Acute Promyelocytic Leukemia