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The t(10;11)(p13-14;q14-21) is a rare but recurring translocation associated with acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Recently the CALM gene was cloned from the t(10;11) breakpoint of U937 and fused to AF10, a putative transcription factor, which had been identified as one of the fusion partners of the MLL gene. In order to define the involvement of these genes in primary leukaemias and cell lines with t(10;11), we analysed the expression of fusion transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR) in five patient samples including ALL, AML and lymphoblastic lymphoma, and three monocytic cell lines (P31/Fujioka, KP-Mo-TS and U937). The CALM-AF10 fusion transcript was detected in all samples; however, the AF10-CALM fusion was not detected in two patient samples and one cell line. In RT-PCR analysis there were six isoforms of the CALM-AF10 fusion transcripts and five of AF10-CALM fusion transcripts. We also detected novel transcripts in U937. Sequence analysis revealed that all these isoforms had in-frame junctions and that some of them resulted from alternative splicing at different exons of CALM and others from different breakpoints at CALM and/or AF10. There were at least two different breakpoints of CALM and three of AF10 gene. Our results suggest that the CALM-AF10 fusion gene is a constant feature and is involved in the pathogenesis of haematological malignancies with t(10;11)(p13-14;q14-21), showing various and often multilineage phenotypes. Thus, t(10;11) needs to be investigated by RT-PCR for identification of the genes involved.

We studied 116 patients (93 children and 23 adults) with acute lymphoblastic leukaemia (ALL) using fluorescence in situ hybridization (FISH) with the yeast artificial chromosome (YAC) clone, 964c10, which includes the recently described ETS-like gene, TEL, on 12p13. FISH revealed that nine of the patients had a t(12 ;21), which had not been previously detected. The nine patients were all children, seven boys and two girls, aged 1-10 years (median 3 years), had an early B immunophenotype, and achieved complete remission, although two of them experienced haematological relapse. In addition to the t(12 :21), FISH also revealed that three of the nine had a del(12p) in the other homolog of chromosome 12 or in the der(12) chromosome itself, and that two others had 12p translocations in the other chromosome 12 homolog. Although chromosomal rearrangements associated with the t(12 ;21) were heterogenous and complex, fusion of the sequences from chromosomes 12 and 21 on the der(21)t(12 ;21) chromosomes was consistent, suggesting that the TEL-AML1 gene fusion on the der(21) chromosome may be critical in leukaemogenesis and that FISH or reverse transcriptase-polymerase chain reaction (RT-PCR) targeted to the chimaeric sequences on the der(21) will be most useful in detecting the t(12 :21) or following a patient with the t(12 ;21), which is one of the most frequent chromosomal rearrangements in both Caucasian and Asian childhood ALL.

Summary. In a study of 23 patients with t(8;21)-associated acute myeloid leukaemia the AML1-MTG8 fusion transcript was present in the majority of serial samples obtained from 17 patients followed for up to 34 months after diagnosis, but was absent in samples from all six patients who had been in continuous complete remission for 61 months after allogeneic bone marrow transplantation (BMT), or for 52, 53, 123,182 and 198 months, respectively, after courses of intensive chemotherapy. Previous studies showed that the AML1-MTG8 fusion transcript was present in most patients with this type of translocation in long-term remission. Our results indicate that blood cells of patients with t(8;21) in remission of over 10 years may not show the AML1-MTG8 fusion transcript, and that those of patients who have undergone allogeneic BMT or intensive chemotherapy may become fusion transcript-negative much earlier. Our study suggests that leukaemic cells with the AML1-MTG8 fusion transcript may survive for some time after courses of chemotherapy or BMT, but that they may eventually be eradicated by immunologic and other antileukaemic mechanisms.