Conventional monitoring strategies for myeloma are not sufficiently sensitive to identify patients likely to benefit from further therapy immediately after transplantation. We have used a sensitive flow cytometry assay that quantitates normal and neoplastic plasma cells to monitor the bone marrow of 45 patients undergoing high-dose chemotherapy. Neoplastic plasma cells were detectable at 3 months after transplantation in 42% of patients. Once detected, neoplastic cell levels increased steadily until clinical progression: these patients had a significantly shorter progression-free survival (PFS) (median, 20 months) than those with no detectable disease (median, longer than 35 months; P ‫؍‬ .003). Neoplastic plasma cells were detectable in 27% (9 of 33) of immunofixation-negative complete-remission patients. These patients had a significantly shorter PFS than immunofixationnegative patients with no detectable neoplastic plasma cells (P ‫؍‬ .04). Normal plasma cells were present in 89% of patients immediately after transplantation, but were not sustained in most cases. Patients with only normal phenotype plasma cells present at 3 months after transplantation and also at second assessment had a low risk of disease progression. Patients with neoplastic plasma cells present at 3 months after transplantation, or with only normal plasma cells present at first assessment and only neoplastic plasma cells at second assessment, had a significantly higher risk of early disease progression (P < .0001) with a 5-year survival of 54% for the high-risk group, compared with 100% in the lowrisk group (P ‫؍‬ .036). Analysis of normal and neoplastic plasma cell levels is more sensitive than immunofixation and can identify which patients may benefit from additional treatment strategies at an early stage after transplantation. (Blood. 2002; 100:3095-3100)

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The plant viruses alfalfa mosaic virus (AMV) and brome mosaic virus (BMV) each divide their genetic information among three RNAs while tobacco mosaic virus (TMV) contains a single genomic RNA. Amino acid sequence comparisons suggest that the single proteins encoded by AMV RNA 1 and BMV RNA 1 and by AMV RNA 2 and BMV RNA 2 are related to the NH2-terminal two-thirds and the COOH-terminal one-third, respectively, of the largest protein encoded by TMV. Separating these two domains in the TMV RNA sequence is an amber termination codon, whose partial suppression allows translation of the downstream domain. Many of the residues that the TMV read-through domain and the segmented plant viruses have in common are also conserved in a read-through domain found in the nonstructural polyprotein of the animal alphaviruses Sindbis and Middelburg. We suggest that, despite substantial differences in gene organization and expression, all of these viruses use related proteins for common functions in RNA replication. Reassortment of functional modules of coding and regulatory sequence from preexisting viral or cellular sources, perhaps via RNA recombination, may be an important mechanism in RNA virus evolution.Viruses with single-stranded RNA genomes that infect higher eukaryotic hosts form a diverse group displaying wide variation in genomic organization (reviewed in ref. 1). The genome of tobacco mosaic virus (TMV), for example, is a single RNA molecule of 6.4 kilobases (kb) (ref. 2; reviewed in ref. 3). It encodes at least four proteins in three open reading frames. That nearest the 5' end contains an in-phase amber termination codon that is partly suppressed during translation in vitro or in vivo to give two products, the larger (known from its molecular weight as p183) being a readthrough extension of the smaller (p126). The template for translation of both of these proteins is the genomic RNA, the two remaining genes being expressed via subgenomic RNAs.The genomes of alfalfa mosaic virus (AMV) and brome mosaic virus (BMV), in contrast, each consist of three RNA segments, termed RNAs 1, 2, and 3 in order of decreasing size (ref. 4-8; reviewed in ref. 9). The two larger RNAs of each virus are monocistronic. The smallest is dicistronic, with the 3' proximal gene in both cases encoding the coat protein that is translated from a subgenomic mRNA. Although both viruses require all three RNAs for infection, AMV, unlike BMV, also requires either coat protein or the subgenomic mRNA for coat. Conversely, all three BMV RNAs, unlike the AMV RNAs, are aminoacylatable with tyrosine. In this respect, the BMV RNAs resemble TMV RNA (which accepts either histidine or valine according to the strain). Each virus has a different morphology, TMV being rod-shaped, AMV bacilliform, and BMV icosahedral.All three viruses are thus clearly distinguished by conventional criteria. Nevertheless, we show in this paper that the amino acid sequences of the proteins encoded by AMV RNA 1 and BMV RNA 1 are strikingly similar both to each other and to that...