Summary. Acute myeloid leukaemia (AML) with the t(8;21)(q22;q22) is deemed to be a 'good-risk' disease. 396 patients with AML at diagnosis were screened for the presence of t(8;21) and AML1/ETO fusion transcripts by cytogenetic and RT-PCR techniques respectively. 32 cases of t(8;21) were detected, all of which were also PCR positive. A further 19 cases were detected at the molecular level, predominantly but not exclusively in M1 and M2 FAB types. Approximately 12% of all new cases of AML are estimated to have AML1/ETO fusion transcripts and it is suggested that molecular screening should be performed in all cases with the possible exception of the M3 FAB type.

Summary. Acute promyelocytic leukaemia (APL) is characterized by the t(15;17) leading to the formation of PMLRARa and RARa-PML fusion genes; this rearrangement has been considered both diagnostic for, and restricted to, this subtype of acute myeloid leukaemia (AML FAB M3). We describe two cases of AML with the t(15;17) associated with a PML/RARa 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 nuclear staining pattern as observed in typical cases of APL with the t(15;17). Similarly, blasts from this case were found to be sensitive to ATRA in vitro as determined by NBT reduction test and by normalization of the PML nuclear body staining pattern. To determine the frequency of PML/RARa rearrangements in FAB subtypes other than M3, 530 patients from the MRC AML trials were screened using nested RT-PCR. Only one individual, initially classified as M5 with a normal karyotype, was found to have a PML/RARa rearrangement. The diagnosis was revised to M3 variant on subsequent morphological 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 current FAB criteria. Therefore, although we consider cytogenetic analysis of newly diagnosed cases of AML to be mandatory, our data suggests that routine molecular screening for PML/ RARa rearrangements is not justified and should be reserved for those cases displaying features which may be suspicious of APL even if such cells comprise only a minority of the total population.

The Bcl10 gene was identified through characterization of the t(1;14)(p22;q32) associated with mucosa‐associated lymphoid tissue (MALT) lymphoma. Bcl10 is implicated in the regulation of apoptosis and has been reported to be mutated in other subtypes of non‐Hodgkin's B‐cell lymphoma (B‐NHL) and leukaemic cell lines, raising the possibility that its deregulation could be implicated in other forms of haematological malignancy. We screened 226 cases, including 123 acute myeloid leukaemia (AML), 50 acute lymphoblastic leukaemia (ALL), 20 chronic myeloid leukaemia (CML), 10 chronic lymphocytic leukaemia–prolymphocytic leukaemia (CLL/PLL) and 23 cases with 1p abnormalities, for Bcl10 mutations by reverse transcription polymerase chain reaction–single‐stranded conformation polymorphism (RT‐PCR/SSCP). Three known polymorphisms and two common splice variants were identified; however, no mutations were detected. One splice variant led to a 33‐bp in frame deletion, whereas the other caused a 16‐bp deletion predicting C‐terminal truncation of Bcl10. However, both splice variants were also detected in normal bone marrow, suggesting that they are unlikely to be of pathogenetic significance. Furthermore, Southern blot analysis revealed no rearrangements of Bcl10 among 16 ALL and 11 cases of haematological malignancy with 1p abnormalities. Our results suggest that mutation of the Bcl10 gene as a mechanism of tumorigenesis is not associated with leukaemia.

Summary. Acute myeloid leukaemia (AML) patients with either a t(15;17), t(8;21) or inv(16) at diagnosis have 'goodrisk' disease with a favourable response to therapy and improved survival. Detection of cryptic fusion genes created by these translocations has been reported where there is no cytogenetic evidence of the corresponding abnormality. It is likely that these cases share the same favourable prognosis. Secondary cytogenetic changes commonly associated with these rearrangements are þ8 with t(15;17), del(9q) with t(8;21) and þ22 with inv(16). These secondary abnormalities are also observed alone, raising the possibility that they may be markers of underlying cryptic rearrangements. In order to determine the frequency of these rearrangements in AML cases with þ8, del(9q) or þ22 we have performed an analysis of 63 such patients in whom there was no evidence of a t(15;17), t(8;21) or inv(16) by cytogenetics. No diseaserelated fusion transcripts were identified, indicating that the secondary changes are rarely markers for cryptic rearrangements.