Acute promyelocytic leukemia (APL) of the M3 subtype is characterized by translocation t(15;17) that generates the PML-RARA fusion gene. Depending on the breakpoint position in the PML gene, 3 main fusion transcripts usually result. These breakpoints are bcr1 and bcr3 in introns 6 and 3, respectively, and bcr2 in exon 6. This report describes a rare atypical bcr2 breakpoint in a patient with morphological, cytogenetic and molecular features of APL. The presence of t(15;17) was first revealed by fluorescent in situ hybridization. Molecular analysis by reverse transcription polymerase chain reaction using primers for different PML-RARA junctions showed bands with different sizes compared with those generated from the three classical breakpoints, namely bcr1, bcr2 and bcr3. However, sequence analysis confirmed the presence of a bcr2 transcript with an atypical breakpoint within exon 6. The patient responded well to treatment and is now in complete remission. However, suggesting a favorable prognosis associated with such a rare transcript is difficult as more similar cases are needed to confirm such a conclusion. This article also stresses the importance of sequencing unusual polymerase chain reaction products to confirm their nature.

Despite the major role of the AKT/PKB family of proteins in the regulation of many growth and survival mechanisms in the cell, and the increasing evidence suggesting that AKT disruption could play a key role in many human malignancies, no major mutations of AKT genes had been reported, until very recently when Carpten et al reported a novel transforming mutation (E17K) in the pleckstrin homology domain of the AKT1 gene in solid tumours. Several laboratories are now screening for this mutation in different malignancies, and, recently, the mutation was described by Malanga et al in 1.9% of lung cancer patients. Considering the importance of the PI3K/AKT pathway in mediating survival and antiapoptotic signals in the B-cell types of chronic lymphocytic leukaemia (CLL) and acute lymphoblastic leukaemia (ALL), we sequenced the AKT1 exon 3 for the above mentioned mutation in 87 specimens, representing 45 CLLs, 38 ALLs and 4 prolymphocytic leukaemia (PLL) cases, which are all of B-cell origin. Our results show that the mutation E17K/AKT1 was not detected in the pleckstrin homology domain of AKT1 of the investigated cases. We conclude that this mutation is not a major event in B-cell-derived lymphoid leukaemias.