<unk>  is characterized by a chromosomal translocation involving the retinoic acid receptor-alpha gene on chromosome 17 (RARA). In 95% of cases of<unk> , retinoic acid receptor-alpha (RARA) gene on chromosome 17 is involved in a reciprocal translocation with the<unk>  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. Eight other rare gene rearrangements have been described in<unk>  fusing RARA to<unk>  leukemia zinc finger (PLZF also known as ZBTB16), nucleophosmin (NPM1), nuclear matrix associated (NUMA1), signal transducer and activator of transcription 5b (STAT5B), protein kinase A regulatory subunit 1α (PRKAR1A), factor interacting with PAPOLA and CPSF1 (FIP1L1), BCL6 corepressor (BCOR) or oligonucleotide/oligosaccharide-binding fold containing 2A (OBFC2A also known as NABP1) genes. Some of these rearrangements are ATRA-sensitive or have unknown sensitivity to ATRA because they are so rare; STAT5B/RARA and PLZF/RARA are known to be resistant to ATRA. The fusion of PML and RARA results in expression of 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 RARA is believed to be the initiating event, additional mutations are required for the development of leukemia. RAR-α/PLZF gene fusion produces a subtype of<unk>  that is unresponsive to tretinoin therapy and less responsive to standard anthracycline chemotherapy hence leading to poorer long-term outcomes in this subset of patients.
Acute promyelocytic leukemia
Prolymphocytic leukemia
Acute megakaryoblastic leukemia
Myeloid leukemia
Acute monocytic leukemia
T-cell leukemia
Monocytic leukemia
Acute erythroid leukemia