Identification of the t(15;17) in AML FAB types other than M3: evaluation of the role of molecular screening for the PML/RAR alpha rearrangement in newly diagnosed AML

Acute promyelocytic leukaemia (APL) is characterized by the t(15;17) leadin g to the formation of PML-RAR alpha and RAR alpha-PML fusion genes; this re arrangement has been considered both diagnostic for, and restricted to, thi s subtype of acute myeloid leukaemia (AML FAB M3). We describe two cases of AML with the t(15;17) associated with a PML/RAR alpha rearrangement which lacked typical APL morphology, classified as FAB M1 and M2 respectively. In both cases morphological review revealed small populations of cells which exhibited some features associated with APL. In the case classified as M1, PML immunofluorescence studies revealed the classic microparticulate nuclea r staining pattern as observed in typical cases of APL with the ttl 5;17), Similarly, blasts from this case were found to be sensitive to ATRA in vitr o as determined by NET reduction test and by normalization of the PML nucle ar body staining pattern. To determine the frequency of PML/RAR alpha rearr angements in FAB subtypes other than M3, 530 patients from the MRC AML tria ls were screened using nested RT-PCR. Only one individual, initially classi fied as M5 with a normal karyotype, was found to have a PML/RAR alpha rearr angement. The diagnosis was revised to M3 variant on subsequent morphologic al review In conclusion, this study demonstrates that, in rare cases, the t (15;17) is not restricted to patients with M3 morphology as defined by curr ent FAB criteria. Therefore, although we consider cytogenetic analysis of n ewly diagnosed cases of AML, to be mandatory, our data suggests that routin e molecular screening for PML/ RAR alpha rearrangements is not justified an d should be reserved for those cases displaying features which may be suspi cious of APL even if such cells comprise only a minority of the total popul ation.