APL had a dismal prognosis before the introduction of new therapies such as anthracyclines in the 1970s followed by the introduction of retinoic acid in 1985s and lately arsenic trioxide in 1994 (de Thé and Chen, 2010; Creutzig et al., 2010; Z. Y. Wang and Chen, 2008). Several chromosomal abnormalities and rearrangement in addition to t(15;17) were seen in 25-40% of APL cases. This includes trisomy 8, del9q and del7q, but not been found to have any impact on prognosis so far (De Botton et al., 2000; Grimwade et al., 2010). Molecular prognostic indicators such as short PML/RARA isoform and FLT3- ITD mutations and presence of aberrant CD expressions such as CD2 or CD9 are found to have an adverse higher risk of relapse (Testa and Lo-Coco, 2016; Montesinos et al., 2011). The initial leukocyte count prior to therapy and older age are negative prognostic factors for survival (Lengfelder et al., 2013).The initial diagnosis of APL should be managed as a clinical emergency due to the possibility of early mortality from haemorrhage, differentiation syndrome and persistence of infection (Choudhry and DeLoughery, 2012). Now, the disease has become the most curable and favourable prognostic subtypes of AML. Recently excellent outcomes have been recorded in clinical trials using no or minimal chemotherapy with a combination of ATRA and ATO based induction (Abedin and Altman, 2016).
Management / Treatment
Until last decade, chemotherapy and radiotherapy were the central dogma in leukaemia therapy to inhibit malignant cell proliferation.
Treatment with ATRA is the immediate frontline treatment when there is a clinical suspicion of APL. This leads to improvement in coagulopathy and reduces the risk of bleeding. ATRA causes a configuration change by binding to the RARA moiety which result in the dissociation of CoCs complex from the receptor. Simultaneously the coactivator complex composed of histone acetylase activity will be recruited and results in opening the chromatin structure relieving the transcriptional repression (Zhou et al., 2007; Zeidan and Gore, 2014). ATRA also induce caspase mediated cleavage of PML-RARA. Further research found ATRA led ubiquitin/proteasome system (UPS) mediated degradation of PML-RARA (Z. Y. Wang and Chen, 2008). ATRA can cause mild side effects such as head ache and arthralgia to serious side effects such as hypotension, cardiac insufficiency, pericardial effusion and pleural effusion (Lee et al., 2013).