The t(8;21)(q22;q22) translocation is a nonrandom chromosomal abnormality frequently found in patients with acute myeloid leukemia (AML) with maturation (M2 subtype). We report here the cloning of a gene, named AMLI, on chromosome 21 that was found to be rearranged in the leukemic cell DNAs from t(8;21) AML patients. The breakpoints in 16 out of 21 patients were clustered within a limited region of AMLI, and detailed analysis in 3 patients revealed that the breakpoints occurred in the same intron ofthe gene. Sequencing of cDNA clones identified a long open reading frame encoding a 250-amino acid protein. Northern blot analysis detected four constant mRNA species in t(8;21) leukemic and normal cells; the largest species was more abundant in the leukemic cells than in normal cells. In addition, two mRNA species limited to the leukemic cells were found. These rmdings indicate that the AMLI gene may be involved in neoplastic transformation of AML with the t(8;21) translocation.
The t(8;21) translocation is one of the most frequent chromosome abnormalities in acute myeloid leukemia. It has been shown that the t(8;21) breakpoints on chromosome 21 cluster within a single specific intron of the AML1 gene, which is highly homologous to the Drosophila segmentation gene runt. Here we report that this translocation juxtaposes the AML1 gene with a novel gene, named MTG8, on chromosome 8, resulting in the synthesis of an AML1‐MTG8 fusion transcript. The fusion protein predicted by the AML1‐MTG8 transcript consists of the runt homology region of AML1 and the most part of MTG8, which contains putative zinc finger DNA binding motifs and proline‐rich regions constituting a characteristic feature of transcription factors. The MTG8 gene is not expressed in normal hematopoietic cells, whereas AML1 is expressed at high levels. Our results indicate that the production of chimeric AML1‐MTG8 protein, probably a chimeric transcription factor, may contribute to myeloid leukemogenesis.
Concurrent chemoradiotherapy using multidrug resistance-nonrelated agents and etoposide is a safe and effective treatment for localized nasal NK/T-cell lymphoma and warrants further investigation.
We agree with Charalambous and Silbermann 1 that action needs to be taken to improve the skills of oncologists to manage chronic cancer pain. Their suggestion for clinical training programs at first seems logical; they cite findings that classroom training did not improve residents' knowledge, 2 a finding consistent with ours, that is, that continuing medical education in cancer pain management seemed to be ineffective. 3 They also cite a study showing that clinically based training in palliative care is effective. 4 In that study, however, there was only a 10% improvement, with statistically significant improvement in only six of 25 questions. In addition, the program was optional, which might suggest that those who took it were more motivated than most, making the generalizability of these findings questionable. Thus, although we agree that change is critically needed, the way to accomplish that change remains elusive. We continue to study this issue and hope that a more complete characterization of this problem will inform the development of more effective programs to support best practices in pain management and palliative care for the broad oncology community.
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