Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunoglobulin (Ig) mutational status in B-cell chronic lymphocytic leukemia (CLL) distinguishes two subsets of patients with different prognosis. Ig status detection is commonly performed with a panel of V(H) family-specific primers. Although this method detects clonal VDJ rearrangement in virtually all cases, it is technically cumbersome and therefore not widely used clinically. Here, we describe a simple and rapid method to establish the mutational status of IgV(H) in CLL. The method is based on a consensus V(H) FR2 primer, used in both polymerase chain reaction (PCR) and sequencing reactions. Overall, monoclonal B-cell populations were detected in 163 of 189 CLL patients (86%). The prognostic value of IgV(H) mutational status was then evaluated by analyzing survival in 146 CLL cases using different V(H) homology cutoffs. CLL prognostic groups were best separated by the classical 98% cutoff: median survival was 127 and 206 months in unmutated and mutated CLL cases, respectively (P = 0.0023). V(H) FR2 consensus and V(H) family PCR were compared in 41 cases, correctly assigning all cases by both methods. Therefore, we suggest a sequential strategy to detect immunoglobulin mutational status in CLL patients by first using the approach described in this study followed by alternative V(H) family-specific PCRs for negative cases.
J Mol Diagn 2005 Nov
PMID:Immunoglobulin mutational status detected through single-round amplification of partial V(H) region represents a good prognostic marker for clinical outcome in chronic lymphocytic leukemia. 1625 54

The flow cytometric classification of CD5-positive small B-cell neoplasms is dependent largely on the differential expression of CD23 and FMC-7. Occasional CD5-positive neoplasms with prominent co-expression of these antigens are encountered, precluding definitive immunophenotypic classification. The authors studied the clinicopathologic features of 26 neoplasms with this indeterminate immunophenotype. Available morphologic material was reviewed and analysis of CYCLIN D1 derangement was performed in selected cases by a combination of immunohistochemical, molecular, and cytogenetic techniques. Individual neoplasms were classified based on correlation of morphologic features and results of CYCLIN D1 studies. The neoplasms were classified into five categories: chronic lymphocytic leukemia (14 cases), "favor chronic lymphocytic leukemia" (3 cases), mantle cell lymphoma (3 cases), lymphoplasmacytic lymphoma (1 case), and unclassifiable (5 cases). Three of the unclassifiable neoplasms had morphologic features of mantle cell lymphoma, but CYCLIN D1 derangement could not be demonstrated. Neither relative expression of CD23 and FMC-7 nor intensity of CD20 or surface immunoglobulin expression was helpful in final classification. The authors conclude that CD5-positive small B-cell neoplasms with an indeterminate immunophenotype are a heterogeneous group, requiring additional studies for final classification. The majority (65%) appear to be chronic lymphocytic leukemia, with most of the remaining cases either definitively mantle cell lymphoma or unclassifiable.
Appl Immunohistochem Mol Morphol 2005 Dec
PMID:CD5-positive B-cell neoplasms of indeterminate immunophenotype: a clinicopathologic analysis of 26 cases. 1628 Jun 59

Phosphorylation analysis of signaling proteins is key for examining intracellular signaling pathways. Conventional biochemical approaches, e.g. immunoprecipitation, Western blot, and ELISA, have played a major role in elucidation of individual signaling events. However, these methods are laborious, time-consuming, and difficult to adapt for high throughput analysis. A multiplex approach to measure phosphorylation state of multiple signaling proteins simultaneously would significantly enhance the efficiency and scope of signaling pathway analysis for mechanistic studies and clinical application. This report describes a novel multiplex microbead suspension array approach to examine phosphoproteomic profiles in lymphoid cells. In the Jurkat T-cell leukemia line, the multiplex assay enabled targeted investigation of phosphorylation kinetics of signal transduction from receptor proximal events (tyrosine phosphoproteins CD3, Lck, Zap-70, and linker for T-cell activation) to cytosolic events (serine/threonine phosphoproteins Erk and Akt) to transcription factors (serine/threonine phosphorylated Rsk, cyclic AMP-response element-binding protein, and STAT3). To broaden the application of the multiplex analysis, signaling pathways were also studied in B-cell lymphoid tumor lines that included chronic lymphocytic leukemia lines. In these cell lines, multiplex suspension array enabled phosphoproteomic analysis of signaling cascade mediated by Syk, a homolog of Zap-70. Results obtained by multiplex analysis were confirmed by immunoprecipitation and Western blot methods. The examples of T-cell and B-cell signaling pathway analyses in this report demonstrate the utility of the multiplex suspension arrays to investigate phosphorylation dynamics and kinetics of several signaling proteins simultaneously in signal transduction pathways.
Mol Cell Proteomics 2006 Apr
PMID:Multiplex analysis of intracellular signaling pathways in lymphoid cells by microbead suspension arrays. 1636 48

Micromet AG and Medlmmune Inc are developing MT-103, a single-chain bispecific recombinant antibody from Micromet's BiTE (bispecific T-cell engager) product platform that binds both the CD19 antigen and the T-cell receptor (CD3), for the potential treatment of B-cell lymphoma. The company is also investigating the compound for the potential treatment of chronic lymphocytic leukemia and acute lymphoblastic leukemia.
Curr Opin Mol Ther 2006 Feb
PMID:MT-103 Micromet/MedImmune. 1650 27

Although the small B-cell lymphomas show major morphologic overlapping, they have been recently shown to be distinct entities with several biologic and clinical differences. Therefore, the utility of a panel of paraffin-reactive antibodies in differentiating these neoplasms was investigated. Using clinical data and morphologic criteria, 134 cases of small B-cell lymphomas were grouped as those with (1) one strongly suggested diagnosis, (2) differential diagnosis between two types of lymphomas, and (3) small B-cell lymphoma without hints for further subclassification. With a panel of antibodies including CD5, CD10, CD23, CD43, bcl-2, and cyclin D1, most but not all cases could be precisely categorized. This panel confirmed the diagnosis in 96.5% of the cases from group 1. In group 2 it confirmed one of the two diagnoses in 81.5% of the cases. In group 3 it established a definitive diagnosis in 55% of the cases. When all groups were considered, a correct diagnosis could be established for 88.1% of cases; for 6.7% of them the authors remained with two possible diagnosis, and the broad "small B-cell lymphoma" was the only diagnosis for 5.2% of cases. CD10 separated most follicular lymphomas from other small B-cell lymphoid neoplasms. CD23 separated small lymphocytic lymphoma/chronic lymphocytic leukemia. Cyclin D1 separated mantle cell lymphoma. The present study selected CD10, CD23, and cyclin D1 as a minimal panel for the classification of small B-cell lymphomas, yielding a final diagnosis in 88.1% of the cases.
Appl Immunohistochem Mol Morphol 2006 Mar
PMID:Contribution of immunohistochemistry to small B-cell lymphoma classification. 1654 Jul 22

This work describes the identification and impact of somatic genomic abnormalities in human chronic lymphocytic leukemia (CLL). Using molecular cytogenetics (FISH) and G-banding cytogenetic analysis, chromosome abnormalities were detected in 37 of 46 (80.4%) CLL patients. 13q14 deletion was the most common finding followed by trisomy 12 and 11q22.3 deletion. 17p13 deletion was also detected as were several less frequent chromosome abnormalities. The presence of these abnormalities significantly influenced the period of treatment-free survival as well as other clinical characteristics. In particular, CLL samples with trisomy 12 and 11q22.3 deletion were associated with shorter treatment-free survival. In order to identify the under-lying molecular differences among CLL subgroups with different chromosome abnormalities, gene expression profiling was performed on a custom DNA microarray consisting of 10,000 human gene-specific oligonucleotides. A gene dosage effect was observed where the expression of genes at the genetic loci of the sites of the somatic genomic abnormality was altered in a fashion according to the type of genomic change. This phenomenon was particularly evident in CLL samples with trisomy 12 and 17p13 deletion. Thus, this study demonstrates that genomic abnormalities influence gene expression in CLL by a dosage effect.
Int J Mol Med 2006 May
PMID:Genomic abnormalities in chronic lymphocytic leukemia influence gene expression by a gene dosage effect. 1659 59

Immunoglobulin kappa (IGK) locus rearrangements were analyzed in parallel on cDNA/genomic DNA in 188 kappa- and 103 lambda-chronic lymphocytic leukemia (CLL) cases. IGKV-KDE and IGKJ-C-intron-KDE rearrangements were also analyzed on genomic DNA. In kappa-CLL, only 3 of 188 cases carried double in-frame IGKV-J transcripts: in such cases, the possibility that leukemic cells expressed more than one kappa chain cannot be excluded. Twenty-eight kappa-CLL cases also carried nonexpressed (nontranscribed and/or out-of-frame) IGKV-J rearrangements. Taking IGKV-J, IGKV-KDE, and IGKJ-C-intron-KDE rearrangements together, 38% of kappa-CLL cases carried biallelic IGK locus rearrangements. In lambda-CLL, 69 IGKV-J rearrangements were detected in 64 of 103 cases (62%); 24 rearrangements (38.2%) were in-frame. Four cases carried in-frame IGKV-J transcripts but retained monotypic light-chain expression, suggesting posttranscriptional regulation of allelic exclusion. In all, taking IGKV-J, IGKV-KDE, and IGKJ-C-intron-KDE rearrangements together, 97% of lambda-CLL cases had at least 1 rearranged IGK allele, in keeping with normal cells. IG repertoire comparisons in kappa- versus lambda-CLL revealed that CLL precursor cells tried many rearrangements on the same IGK allele before they became lambda producers. Thirteen of 28 and 26 of 69 non-expressed sequences in, respectively, kappa- or lambda-CLL had < 100% homology to germline. This finding might be considered as evidence for secondary rearrangements occurring after the onset of somatic hypermutation, at least in some cases. The inactivation of potentially functional IGKV-J joints by secondary rearrangements indicates active receptor editing in CLL and provides further evidence for the role of antigen in CLL immunopathogenesis.
Mol Med
PMID:Analysis of expressed and non-expressed IGK locus rearrangements in chronic lymphocytic leukemia. 1662 20

Aims-To directly visualise immunoglobulin (Ig) heavy (H) and light chain genes (kappa and lambda) in metaphase chromosomes and interphase nuclei of normal and malignant lymphocytes using small genomic probes targeted to intragenic sequences.Methods-Cytogenetic preparations from phytohaemagglutinin stimulated lymphocytes, B-chronic lymphocytic leukaemia (B-CLL) cells, and a B-prolymphocytic leukaemia (B-PLL) cell line, containing a t(11;14), were hybridised in situ using biotin or digoxigenin labelled plasmid probes. The kappa genes were visualised with a combination of probes for the Ckappa, Jkappa, Vkappa1, and Vkappa2 segments, the lambda genes with a probe containing the Jlambda2-Clambda2, Jlambda3-Clambda3 segments and the H genes with a probe for Clambda2. Hybridisation sites were visualised using appropriate fluorochrome conjugates and images were analysed by digital microscopy.Results-In both normal and malignant lymphoid cells, the kappa and lambda genes were visualised as a single dot signal, whereas the H lambda genes were resolved as either two or three separate signals per chromatid in metaphase chromosomes or per allele in interphase nuclei. In the malignant PLL cells, double hybridisation experiments with a painting library specific for the chromosome 11 showed that the lambda region was retained in the translocated chromosome, with an in situ resolution pattern similar to that of the normal allele.Conclusions-This study shows that a high resolution in situ analysis of the three Ig loci can be efficiently performed with small size genomic probes on both normal and malignant lymphoid cells. Such an approach offers a flexible tool for the molecular characterisations of these loci on chromosomes and individual neoplastic cells.
Clin Mol Pathol 1995 Jun
PMID:In situ visualisation of immunoglobulin genes in normal and malignant lymphoid cells. 1669 98

The precise diagnosis of lymphoma usually requires the histological examination of lymph nodes or involved tissues. Mantle cell lymphoma is a form of intermediate grade non-Hodgkin's lymphoma in which typical morphological immunophenotypic and cytogenetic features have been recognised. A case of leukaemic mantle cell lymphoma with the characteristic reciprocal translocation t(11;14) together with trisomy 12, a chromosomal abnormality usually associated with B cell chronic lymphocytic leukaemia (CLL), is presented. This combination of cytogenetic abnormalities has not been reported previously. The lack of lymphadenopathy and hepatosplenomegaly in this patient is more in keeping with stage A0 CLL. This case demonstrates the close clinical and biological relationship between mantle cell lymphoma and CLL.
Clin Mol Pathol 1995 Jun
PMID:Leukaemic mantle cell lymphoma with t(11;14) and trisomy 12 showing clinical features of state A0 B cell chronic lymphocytic leukaemia. 1669 99

Aims-To study correlations between the pattern of silver stained nucleolar organiser regions (AgNORs) in chronic lymphocytic leukaemia (CLL) and parameters of tumour kinetics. To investigate whether quantitation of the AgNOR pattern can be used to discriminate between patients with stable and progressive disease.Methods-Peripheral blood smears from 48 patients with CLL, classified as having either stable or progressive disease (Rai stage III or IV; bulky lymph nodes or massive splenomegaly; or peripheral lymphocytes >100 x 10(9)/1), were studied. For each patient, total tumour mass (TTM) and for patients undergoing a period of observation without treatment, the TTM duplication time (DT) and the lymphocyte doubling time (LDT) were calculated.Results-Four cell types could be distinguished according to their AgNOR pattern: (1) cells with a single cluster; (2) cells with a single compact nucleolus; (3) cells with two compact nucleoli; and (4) cells with several scattered dots. The percentage of cells with clusters was the AgNOR parameter which correlated best with TTM and LDT. Correlations were also seen between the proportion of cells with clusters and age and haemoglobin concentration. A significant correlation with DT could be detected only when age was kept constant. Linear discriminant analysis revealed that the percentage of cells with clusters was the most important prognostic factor. This alone classified 94% of the patients correctly (jackknive procedure) as either stable or progressive CLL.Conclusions-The percentage of circulating lymphocytes with clusters of AgNORs can be used as a parameter of tumour kinetics in CLL and helps to discriminate between patients with stable and progressive disease. For practical purposes, a value of more than 13% of cells with clusters is suggestive of progressive disease.
Clin Mol Pathol 1996 Dec
PMID:AgNOR clusters as a parameter of cell kinetics in chronic lymphocytic leukaemia. 1669 3


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>