ABSTRACT
During 2001 and 2002, Pisum sativum var. vulgare plants grown as commercial crops in Almeria (southeast Spain) showed vein clearing and chlorotic mottle of leaves, leaf deformation, flower abortion, necrotic mottle and deformation of pods, and stunted plant growth. Crude sap of collected plants was mechanically inoculated on healthy pea plants which reproduced symptoms observed in the field; local necrotic lesions were produced on mechanically infected Chenopodium quinoa, C. amaranticolor, and Gomphrena globosa, systemic mosaic symptoms on Brassica napus and Nicotiana benthamiana, and local lesions plus systemic mosaic symptoms on N. clevelandii, which are all characteristic of Turnip mosaic virus (TuMV) (1). A reverse transcription-polymerase chain reaction assay using general primers for the extreme 3' end of the potyvirus genome amplified products of 750 and 1,700 bp in nucleic acid extracts from naturally infected pea plants as well as from the mechanically infected test plants. The overlapping nucleotide sequences of the products (GenBank Accession No. AJ489259) had a nucleotide sequence identity of 86.5% and a derived amino acid identity of 95.0% with several published sequences of TuMV (1). This report cites the first partial nucleotide sequence of TuMV infecting pea crops, and although natural infections of this virus in pea have been reported in Morocco (1976) and in the United States (2), to our knowledge, this is the first report of TuMV in Spain. References: (1) P. Lehmann et al. Physiol. Mol. Plant Pathol. 51:195, 1997. (2) R. Provvidenti. Plant Dis. Rep. 62:482, 1978.
ABSTRACT
Chronic myeloid leukemia (CML) progresses from a chronic to a blastic phase where the leukemic cells are proliferative and undifferentiated. The CML is nowadays successfully treated with BCR-ABL kinase inhibitors as imatinib and dasatinib. In the CML-derived K562 cell line, low concentrations of imatinib induce proliferative arrest and erythroid differentiation. We found that imatinib upregulated the cell cycle inhibitor p27(KIP1) (p27) in a time- and -concentration dependent manner, and that the extent of imatinib-mediated differentiation was severely decreased in cells with depleted p27. MYC (c-Myc) is a transcription factor frequently deregulated in human cancer. MYC is overexpressed in untreated CML and is associated to poor response to imatinib. Using K562 sublines with conditional MYC expression (induced by Zn(2+) or activated by 4-hydroxy-tamoxifen) we show that MYC prevented the erythroid differentiation induced by imatinib and dasatinib. The differentiation inhibition is not due to increased proliferation of MYC-expressing clones or enhanced apoptosis of differentiated cells. As p27 overexpression is reported to induce erythroid differentiation in K562, we explored the effect of MYC on imatinib-dependent induction of p27. We show that MYC abrogated the imatinib-induced upregulation of p27 concomitantly with the differentiation inhibition, suggesting that MYC inhibits differentiation by antagonizing the imatinib-mediated upregulation of p27. This effect occurs mainly by p27 protein destabilization. This was in part due to MYC-dependent induction of SKP2, a component of the ubiquitin ligase complex that targets p27 for degradation. The results suggest that, although MYC deregulation does not directly confer resistance to imatinib, it might be a factor that contributes to progression of CML through the inhibition of differentiation.