TP53 mutation is an independent marker of poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP) therapy. However, its prognostic value in the rituximab immunochemotherapy era remains undefined. In the present study of a large cohort of DLBCL patients treated with rituximab plus CHOP (R-CHOP), we show that those with TP53 mutations had worse overall and progression-free survival compared with those without. Unlike earlier studies of patients treated with CHOP, TP53 mutation has predictive value for R-CHOPtreated patients with either the germinal center B-cell or activated B-cell DLBCL subtypes. Furthermore, we identified the loop-sheet-helix and L3 motifs in the DNAbinding domain to be the most critical structures for maintaining p53 function. In contrast, TP53 deletion and loss of heterozygosity did not confer worse survival. If gene mutation data are not available, immunohistochemical analysis showing > 50% cells expressing p53 protein is a useful surrogate and was able to stratify patients with significantly different prognoses. We conclude that assessment of TP53 mutation status is important for stratifying R-CHOP-treated patients into distinct prognostic subsets and has significant value in the design of future therapeutic strategies. (Blood. 2012;120(19):3986-3996)
Rice blast, caused by the fungal pathogen Magnaporthe grisea, is one of the most devastating diseases in rice worldwide. The dominant resistance gene, Pi-d2 [previously named Pi-d(t)2], present in the rice variety Digu, confers gene-for-gene resistance to the Chinese blast strain, ZB15. Pi-d2 was previously mapped close to the centromere of chromosome 6. In this study, the Pi-d2 gene was isolated by a map-based cloning strategy. Pi-d2 encodes a receptor-like kinase protein with a predicted extracellular domain of a bulb-type mannose specific binding lectin (B-lectin) and an intracellular serine-threonine kinase domain. Pi-d2 is a single-copy gene that is constitutively expressed in the rice variety Digu. Transgenic plants carrying the Pi-d2 transgene confer race-specific resistance to the M. grisea strain, ZB15. The Pi-d2 protein is plasma membrane localized. A single amino acid difference at position 441 of Pi-d2 distinguishes resistant and susceptible alleles of rice blast resistance gene Pi-d2. Because of its novel extracellular domain, Pi-d2 represents a new class of plant resistance genes.
SummaryRice tillering is an important agronomic trait for grain production. The HIGH-TILLERING DWARF1 (HTD1) gene encodes an ortholog of Arabidopsis MAX3. Complementation analyses for HTD1 confirm that the defect in HTD1 is responsible for both high-tillering and dwarf phenotypes in the htd1 mutant. The rescue of the Arabidopsis max3 mutant phenotype by the introduction of Pro 35S :HTD1 indicates HTD1 is a carotenoid cleavage dioxygenase that has the same function as MAX3 in synthesis of a carotenoid-derived signal molecule. The HTD1 gene is expressed in both shoot and root tissues. By evaluating Pro HTD1 :GUS expression, we found that the HTD1 gene is mainly expressed in vascular bundle tissues throughout the plant. Auxin induction of HTD1 expression suggests that auxin may regulate rice tillering partly through upregulation of HTD1 gene transcription. Restoration of dwarf phenotype after the removal of axillary buds indicates that the dwarfism of the htd1 mutant may be a consequence of excessive tiller production. In addition, the expression of HTD1, D3 and OsCCD8a in the htd1 and d3 mutants suggests a feedback mechanism may exist for the synthesis and perception of the carotenoid-derived signal in rice. Characterization of MAX genes in Arabidopsis, and identification of their orthologs in pea, petunia and rice indicates the existence of a conserved mechanism for shoot-branching regulation in both monocots and dicots.
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