In PML, all of the following are seen except -
Acute promyelocytic leukemia (APML, APL) is a subtype of acute myeloid leukemia (AML), a cancer of the white blood cells. In APL, there is an abnormal accumulation of immature granulocytes called promyelocytes. The disease is characterized by a chromosomal translocation involving the retinoic acid receptor alpha (RARa or RARA) gene and is distinguished from other forms of AML by its responsiveness to all-trans retinoic acid (ATRA; also known as tretinoin) therapy. Acute promyelocytic leukemia was first characterized in 1957 by French and Norwegian physicians as a hyperacute fatal illness,with a median survival time of less than a week.Today, prognoses have drastically improved; 10-year survival rates are estimated to be approximately 80-90% according to one study Acute promyelocytic leukemia is characterized by a chromosomal translocation involving the retinoic acid receptor-alpha gene on chromosome 17 (RARA). In 95% of cases of APL, retinoic acid receptor-alpha (RARA) 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. Eight other rare gene rearrangements have been described in APL fusing RARA to promyelocytic 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 1a (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-a/PLZF gene fusion produces a subtype of APL 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 Ref Davidson 23rd edition pg 922
Retinoic acid is used in treatment
15/17 translocation may be seen
CD 15/34 both seen in same cell
Associated with Disseminated intravascular coagulation (DFVC)
Haematology