The translocation (6;9)(p23;q34) in acute nonlymphocytic leukemia results in the formation of a highly consistent dek-can fusion gene. Translocation breakpoints invariably occur in single introns of dek and can, which were named icb-6 and icb-9, respectively. In a case of acute undifferentiated leukemia, a breakpoint was detected in icb-9 of can, whereas no breakpoint could be detected in dek. Genomic and cDNA cloning showed that instead of dek, a different gene was fused to can, which was named set. set encodes transcripts of 2.0 and 2.7 kb that result from the use of alternative polyadenylation sites. Translocations are the best-studied nonrandom chromosomal aberrations associated with specific subtypes of leukemia. As a result of a translocation, an oncogene can be activated through alterations in regulatory DNA sequences that leave the encoded protein intact (e.g., myc) or through formation of a fusion gene, encoding a chimeric protein (e.g., bcr-abl). The t(9;22) associated with chronic myeloid leukemia, acute myeloid leukemia (AML), and acute lymphoblastic leukemia (29) results in the expression of a chimeric BCR-ABL protein with enhanced tyrosine kinase activity (16,19,27,38,45). Pendergast et al. showed that defined sequences encoded by the first exon of bcr interact with the SH2 domain of ABL (33). This interaction is essential for the activation of the ABL tyrosine kinase activity and for the transforming capacity of BCR-ABL. More recently, other fusion genes have been isolated. t(1;19), occurring in childhood pre-B-cell acute leukemia, fuses the E2a gene, encoding transcription factors E12 and E47, to a novel homeobox gene, PBX1 (26, 32). t(15;17), strongly associated with acute promyelocytic leukemia, fuses part of the retinoic acid receptor type a gene (RARt) to a novel gene on chromosome 15 named PML, which is predicted to be a transcription factor (9, 25). bcr-abl, E2A-pbx, andpml-RARao seem to be highly consistent partners.Previously we reported the cloning of t(6;9) breakpoints (43). t(6;9) is the hallmark of a specific subtype of AML characterized by a poor prognosis and a young age of onset. It is classified in the French-American-British system mostly as M2/M4 and rarely as Ml or refractive anemia with excess of blast cells (RAEB) (2,36,39). On chromosome 9, break-* Corresponding author.points take place in a specific intron, icb-9, of a large gene (>140 kb) named Cain (can) (43). On chromosome 6, breakpoints also occur in a single intron, icb-6, of a gene named dek (42). The result of t(6;9) is the formation of a dek-can fusion gene on chromosome 6p-, which is transcribed into an invariable, 5.5-kb, leukemia-specific dek-can mRNA (39). The fusion transcript encodes a 165-kDa chimeric protein, which derives from the in-frame fusion of dek and can open reading frames (ORFs). Sequence comparison of DEK and CAN with entries in the EMBL data base shows no homology to any known protein sequences. CAN contains several putative dimerization motifs, and the C-terminal part may function as an ancillar...

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The translocation (6;9)(p23;q34) in acute nonlymphocytic leukemia results in the formation of a highly consistent dek-can fusion gene. Translocation breakpoints invariably occur in single introns of dek and can, which were named icb-6 and icb-9, respectively. In a case of acute undifferentiated leukemia, a breakpoint was detected in icb-9 of can, whereas no breakpoint could be detected in dek. Genomic and cDNA cloning showed that instead of dek, a different gene was fused to can, which was named set. set encodes transcripts of 2.0 and 2.7 kb that result from the use of alternative polyadenylation sites. Both transcripts contain the open reading frame for a putative SET protein with a predicted molecular mass of 32 kDa. The set-can fusion gene is transcribed into a 5-kb transcript that contains a single open reading frame predicting a 155-kDa chimeric SET-CAN protein. The SET sequence shows homology with the yeast nucleosome assembly protein NAP-I. The only common sequence motif of SET and DEK proteins is an acidic region. SET has a long acidic tail, of which a large part is present in the predicted SET-CAN fusion protein. The set gene is located on chromosome 9q34, centromeric of c-abl. Since a dek-can fusion gene is present in t(6;9) acute myeloid leukemia and a set-can fusion gene was found in a case of acute undifferentiated leukemia, we assume that can may function as an oncogene activated by fusion of its 3' part to dek, set, or perhaps other genes.

Interstitial pneumonia after allogeneic bone marrow transplantation is frequently associated with human cytomegalovirus (HCMV) infection. However, in a considerable proportion of the cases, no infectious agent can be determined and the interstitial pneumonia is then classified as idiopathic. Hypothetically, idiopathic interstitial pneumonia could be caused by HCMV present in such small amounts or such conformation that the virus cannot be detected by routine histopathologic analysis or viral culture techniques. To check this hypothesis, three sensitive methods for HCMV detection (in situ hybridization, the polymerase chain reaction for HCMV-DNA detection, and immunohistochemistry for the detection of HCMV immediate early antigens) have been applied on lung tissue sections of bone marrow transplant patients who died with interstitial pneumonia. Three categories were distinguished: (1) patients with HCMV-related interstitial pneumonia (n = 5); (2) patients with idiopathic interstitial pneumonia (n = 10); and (3) patients with HCMV interstitial pneumonia who had been treated with antiviral therapy (n = 2). In the first category, all three techniques yielded clearly positive results, whereas these techniques indicated that one of the patients of the second category had HCMV-related pneumonia. In the third category no positive signals could be obtained. The presented data indicate that a direct involvement of HCMV in idiopathic interstitial pneumonia is unlikely. However, a PCR performed for Epstein-Barr virus (EBV) was positive in two patients with idiopathic interstitial pneumonia. These data indicate that the introduction of new sensitive techniques such as in situ hybridization, immunohistochemistry, and the polymerase chain reaction revives the interest for HCMV and other causative infectious agents in idiopathic interstitial pneumonia.

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