The diagnosis of APL is primarily based on the peripheral blood film and marrow aspirate, but cytogenetic studies will reveal that the vast majority of patients with APL have a balanced translocation between chromosomes 15 and 17 (t[15,17]).
The breakpoints for this translocation are highly conserved to two regions on chromosome 15 and a single region on 17. The 15 breakpoint disrupts a gene called pml which codes for a protein which is probably a transcription factor. The 17 breakpoint disrupts the gene for the retinoic acid receptor-alpha, which is a nuclear receptor (part of the steroid-thyroid superfamily).
t[15,17] results in a hybrid protein PML/RAR which blocks differentiation of the promyelocyte. The precise mechanism is unclear, but is most likely to be due to alteration of PML action. This is supported by immunofluorescence studies which show that the nuclear organisation of PML/RAR is different to that of PML. It is therefore postulated that the precise location of transcription factors in the nucleus affects their function, to the extent of blocking cell differentiation.
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