Gene expression profiling of pulmonary mucosa-associated lymphoid tissue lymphoma identifies new biologic insights with potential diagnostic and therapeutic applications.
ABSTRACT We conducted comprehensive gene expression profiling (GEP) of primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma (n = 33) and compared the results to GEP of other B- and T-cell lymphomas and normal lymphocytes to identify novel markers and deregulated pathways. MALT has a prominent T-cell signature and a marginal zone/memory B-cell profile. Four novel transcripts were specifically overexpressed in MALT, and 2 of these, MMP7 and SIGLEC6, were validated at the protein level. GEP also revealed distinct molecular subsets in MALT. One subset, characterized by MALT1 translocations, showed overexpression of nuclear factor-kappaB (NF-KB) pathway genes but also was enriched for chemokine signaling pathways. Another subset showed increased plasma cells and a prominent plasma cell gene signature. By analyzing several genes with very high ("spiked") expression in individual cases, we identified clusters with different biologic characteristics, such as samples with MALT1 translocations having high expression of MALT1 and RARA, samples with plasmacytic differentiation having high FKBP11 expression, and samples with high RGS13 expression tending to have trisomy 3 and reactive follicles. In conclusion, MALT subgroups with distinct pathologic features defined by distinct groups of deregulated genes were identified. These genes could represent novel diagnostic and therapeutic targets.
Article: Substitution of a single amino acid in the 2b protein of Pea early-browning virus affects nematode transmission.[show abstract] [hide abstract]
ABSTRACT: The 2b protein of Pea early-browning virus (PEBV) is required for transmission of the virus by nematodes. Comparison of the 2b proteins of highly transmissible (TpA56) and poorly transmissible (SP5) isolates of PEBV identified two amino acid substitutions (G90S and G177R) that might be responsible for the poor transmission of isolate SP5. Hybrid viruses were created in which the TpA56 2b protein carried SP5-specific substitutions at residue 90 or 177, and in which the SP5 2b protein carried TpA56-specific substitutions at these positions. Transmission tests showed that the G177R substitution is sufficient to prevent nematode transmission of the virus. Examination of the 2b proteins from PEBV and other tobraviruses predicted the presence of a coiled-coil domain in the central region of the protein. This structural element is important for the association of interacting proteins and, thus, might mediate interaction of the 2b protein with the virus coat protein or with the vector nematode.Journal of General Virology 08/2002; 83(Pt 7):1771-5. · 3.36 Impact Factor
Article: Identification and molecular cloning of p75/AIRM1, a novel member of the sialoadhesin family that functions as an inhibitory receptor in human natural killer cells.[show abstract] [hide abstract]
ABSTRACT: In this study, by the generation of a specific monoclonal antibody, we identified p75/AIRM1 (for adhesion inhibitory receptor molecule 1), a novel inhibitory receptor that is mostly confined to human natural killer cells. p75/AIRM1 is a 75-kD glycoprotein that, upon sodium pervanadate treatment, becomes tyrosine phosphorylated and associates to src homology 2 domain-bearing protein tyrosine phosphatase (SHP)-1. The p75/AIRM1 gene is located on human chromosome 19 and encodes a novel member of the sialoadhesin family characterized by three immunoglobulin-like extracellular domains (one NH(2)-terminal V-type and two C2-type) and a classical immunoreceptor tyrosine-based inhibitory motif (ITIM) in the cytoplasmic portion. The highest amino acid sequence similarity has been found with the myeloid-specific CD33 molecule and the placental CD33L1 protein. Similar to other sialoadhesin molecules, p75/AIRM1 appears to mediate sialic acid-dependent ligand recognition.Journal of Experimental Medicine 10/1999; 190(6):793-802. · 13.85 Impact Factor