Acute Promyelocytic Leukaemia (APL) is an M3 subtype of acute myeloid leukaemia (AML) and is characterized by unique features different from other type of acute myeloid leukaemias. It comprises of 10-17% of all cases of acute myeloid leukaemias. The most common clinical sign at diagnosis in most patients is haemorhagic episodes caused by coagulopathy. It is also characterized by t(15, 17) translocation, severe thrombocytopenia and increased hypergranular promyelocytes on peripheral blood film and bone marrow.
The t(15, 17) is a hallmark for APL and this translocation resulted in balance fusion translocation leads to the formation of an abnormal fusion of promyelocytic leukaemia (PML) and retinoic acid receptor protein known as promyelocytic retinoic acid receptor alpha (PML- RARα). The RARα gene is bound by nuclear corepressor factor in the absence of retinoic acid leading to transcriptional repression. However, the RARα gene is activated in the presence of retinoic acid which causes differentiation of promyelocytes. In APL, the fusion is commonly caused by breakpoints in intron 2 of RARA and any one of the three breakpoint cluster regions in PML, intron 6 (Bcr1), exon 6 (Bcr2) or intron 3 (Bcr3) leading to long, variable and short isoforms respectively.
We recently described the results of differentially expressed miRNA and mRNA in APL. This analysis was performed by using a digital colour-coded barcode technology, NanoString nCounter platform. Gene expression pathway-based analysis was conducted on APL patients using the nCounter® Pan Cancer Pathways Panel (NanoString Technologies, USA) This study involved the expression level of 730 genes and 13 canonical pathways. Furthermore, mutation analysis of FLT3/ITD and NPM1 genes were also performed on the newly diagnosed APL patients.
From the miRNA analyses, 11 miRNA that differentiate APL patients from healthy controls were identified in which six miRNA were up-regulated while the remaining five were down-regulated. . Gene expression pathway-based analysis conducted revealed 90 differentially deregulated genes, in which 30 were up-regulated and 60 were down-regulated in the newly diagnosed APL patients. This study involved the expression level of 730 genes and 13 canonical pathways. Differential pathway expression revealed that pathways involved were transcriptional misregulation, MAPK, RAS and Notch signalling pathways. Mutation analysis of FLT3/ITD revealed 27% mutation within exon 14 of FLT3/ITD
Analysis of these new markers such as miRNA and gene expression as well as DNA mutation suggests more areas need further exploration to assess their interactions and clinical significance. Furthermore, the expression of mRNA and microRNA genes was reported to differ between cases at diagnosis and at relapse in a statistically significant manner,thus representing potential identified risk factors that may assist in patients' management.