Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is generally accepted that patients with chronic myelogenous leukemia in chronic phase under the age of 50 years who have HLA-identical siblings, should be offered bone marrow transplantation within the first year of diagnosis. The projected disease-free survival for these patients is 70% to 80% at 4 years, and most of these will prove to have been cured. Results of bone marrow transplantation for patients with more advanced disease are less promising. For transplant conditioning there is no important difference between cyclophosphamide plus total-body irradiation and busulphan plus cyclophosphamide. Nonenlarged spleens require neither splenectomy nor additional radiotherapy. The use of cyclosporine and methotrexate is currently the optimal approach to graft-versus-host disease prevention. Fewer good results are obtained with "matched" volunteer marrow donors. Use of the polymerase chain reaction to monitor residual BCR-ABL transcripts after bone marrow transplantation may prove useful in identifying patients at increased risk for relapse. Autografting may offer the prospect of prolonged life or even cure for patients without suitable allogeneic donors.
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PMID:Bone marrow transplantation for chronic myelogenous leukemia. 159

Chronic myeloid leukaemia, a clonal myeloproliferative disorder with a biphasic nature, is characterised by a specific chromosomal aberration, the Philadelphia (Ph) chromosome. The Ph chromosome is the result of a reciprocal translocation between chromosomes 9 and 22 and involves the ABL and BCR genes resulting in a chimeric mRNA encoding a specific protein, termed P210. At present, there is no convincing evidence that to maintain the leucocyte count within the normal range prolongs the duration of the stable chronic phase or of survival, and the objectives of treatment are simply to alleviate symptoms or to delay their onset. It has, however, become clear that bone marrow transplantation performed during the chronic phase using an HLA-identical sibling donor offers the best chance of a cure.
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PMID:Chronic leukaemias: can they be cured? Part 1: Chronic myeloid leukaemia. 262 42

Peripheral blood lymphocytes from 9 monoclonal gammopathies of undetermined significance (MGUS) and 27 multiple myelomas (MM) were studied with a panel of monoclonal antibodies (MoAb) that recognize B and T lymphocytes and plasma cells. No difference in the percentage of B lymphocytes, identified by B1 and B4 MoAb, was observed in MGUS and MM patients versus normal controls. However, high percentages of circulating lymphocytes expressing plasma cell-associated antigens were detected in MM (HAN-PC1+ = 29.4 +/- 20.4%; TEC-T10+ = 27.8 +/- 19.2%) whereas they were in the normal range in MGUS (HAN-PC1+ = 8.8 +/- 5.8% p = 0.006; TEC-T10+ = 5.7 +/- 4.7% p less than 0.001). Almost identical results were obtained using PCA-1 MoAb in 17 of these patients. TEC-T10+ and PCA-1+ lymphocytes were sorted and re-analyzed with phycoerythrin conjugated MoAb in 3 healthy subjects, 2 MGUS, and 4 MM patients. In normal subjects and in MGUS the majority of PCA-1+ cells belonged to the B lineage (Leu 2-, Leu3-, Leu 15-, HLA-Dr+), whereas the majority of TEC-T10+ cells are represented by activated T cells and NK cells (Leu 15+). In MM an abnormal expansion of T lymphocytes was chiefly responsible for the high values of lymphocytes expressing plasma cell-associated antigens. Moreover, in MM a clinical evaluation showed a correlation between the presence of these lymphocytes and an aggressive disease. Indeed, they can be considered a useful prognostic marker.
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PMID:Human myeloma: several subsets of circulating lymphocytes express plasma cell-associated antigens. 336 19

In chronic myeloid leukemia (CML) the proto-oncogene c-abl from chromosome 9 q34 is translocated to the breakpoint cluster region (bcr) gene on chromosome 22 q11. This translocation results in a BCR-ABL fusion gene, which encodes chimeric fusion oncoproteins p210BCR-ABL. Here we demonstrate that a peptide with joining region sequence ATGFKQSSKALQRPVAS (eight amino acids (aa) encoded by BCR exon 3; one novel lysine, encoded by the fusion codon; eight aa encoded by ABL exon 2) is immunogenic to human T cells. Primary immune response induction with this peptide resulted in a HLA DR2(DRB1*1501) restricted CD4+ BCR-ABL peptide specific T cell line P1. Responses of P1 were negatively affected by individual aa replacement by alanine at eight aa positions within the 17mer peptide (F4, K5, Q6, K9, L11, Q12, R13, P14). These findings were supported by experiments with a panel of overlapping 11mer b3a2 peptides. Only two of these peptides with an aa sequence encompassing all residues which could not be replaced by alanine induced P1 proliferation. Since presentation of cytosolic oncoproteins as peptides by DR molecules has been observed, the present findings provide a possible explanation for post interferon-alpha persisting remissions in spite of the presence of BCR-ABL PCR positive progenitors.
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PMID:Recognition of peptides corresponding to the joining region of p210BCR-ABL protein by human T cells. 764 23

A newly established human leukemia cell line, OM9;22, is reported, with B-precursor immunophenotype (CD10+ CD19+ CD22+ HLA- DR+ C mu-) and CD13 antigen, originated from a 19-year-old female patient with Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL). The OM9;22 cells carry a Philadelphia (Ph) translocation and hybrid message detected by a minor-breakpoint cluster region (BCR) exon 1/ABL exon 2 junctional probe using reverse transcriptase polymerase chain reaction. The genetic alterations are consistent with those observed in the donor's leukemia cells, allowing us to conclude that this cell line is a minor-BCR rearranged Ph-positive ALL (Ph+ ALL). Colony formation of the OM9;22 cells in methylcellulose culture is enhanced by the addition of human interleukin 7 (IL-7). In liquid culture, more than 80% of IL-7-treated OM9;22 cells express CD20 antigen but fail to express surface immunoglobulins or cytoplasmic mu-chain, indicating that the cells have a potential of limited maturation by IL-7. By contrast, IL-4 suppresses the colony formation of the OM9;22 cells. These findings suggest that this cell line might be a model of B-precursor human leukemia with proliferative capability by IL-7.
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PMID:Interleukin-7 enhances colony growth and induces CD20 antigen of a Ph+ acute lymphoblastic leukemia cell line, OM9;22. 768 4

A quadruplex reaction has been developed which amplifies the short tandem repeat (STR) loci HUM-VWA31/A, HUMTHO1, HUMF13A1 and HUMFES/FPS. Detection of the PCR products employs denaturing polyacrylamide gels coupled with fluorescent-based technology. This system has been evaluated for use in routine forensic casework and has been shown to be both robust and reproducible. The quadruplex reaction is as sensitive as the commercially available HLA DQ alpha Amplitype typing system and can be used on both degraded and aged material. The problems of environmental contamination have been shown to be limited provided strict procedural practices are followed-i.e. physical separation of sample extraction and amplified products; the use of dedicated equipment such as pipettes; the separation of amplification preparation area. The ability of the system to detect mixtures and the successful analysis of case stains has shown that this system is well suited as a tool for forensic investigation.
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PMID:The validation of short tandem repeat (STR) loci for use in forensic casework. 781 23

The clinical status of a homogeneous cohort of long-term survivors of allogeneic marrow transplantation was assessed and residual leukaemia was studied by reverse transcription polymerase chain reaction for leukaemia specific BCR-ABL mRNA. The group comprised 34 consecutive patients with CML in chronic phase treated by chemoradiotherapy and transplantation of bone marrow from HLA-identical sibling donors between February 1981 and December 1983 in the joint Hammersmith-Northwick Park programme. The probability of survival at 10 years was 59 +/- 17%. Eighteen of the 19 surviving (95%) patients have Karnofsky scores of 90 or 100% indicative of a good performance status. One of the survivors had evidence of relapse 6.5 years after transplant but has since been restored to complete remission by treatment with interferon-alpha followed by donor leucocyte transfusions. Surprisingly, 2 of the 19 patients who have been in remission for over 10 years have molecular evidence of persisting leukaemic cells. Quantification by competitive PCR indicated that the malignant clone persisted at low levels. The data suggest that the majority of long-term survivors after BMT for CML are in good health and may be regarded as cured. Some long-term survivors, however, may still harbour residual leukaemic cells and continued monitoring for late relapse is warranted. Late relapse is amenable to further therapy with leukocyte transfusions from the original marrow donor.
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PMID:Detection of residual leukaemia more than 10 years after allogeneic bone marrow transplantation for chronic myelogenous leukaemia. 785 36

The genetic analysis of ancient populations through DNA from bone remains, requires use of short sized loci that can be amplified by polymerase chain reaction (PCR) for which the short tandem repeat (STR) loci are most suitable. These techniques can also be applied to genetic identification in forensic casework. In this study three STR loci, HUMFES/FPS, HUMTH01, and HUMVWA31A, were selected to estimate their usefulness when applied to recent and ancient spongy bone DNA typing. In addition, loci D1S80 and HLA DQ alpha were also tested in the analysis of recent spongy bone DNA. The recent remains studied were constituted by ten spongy bone samples of postmortem material from one individual buried for 1 year. The ancient remains are composed by 8 spongy bone samples from the heads of left femurs from a XII-XIII Centuries Basque Country population. Adequate amplification and typing results could only be obtained with cetyltrimethyl ammonium bromide (CTAB)-extracted DNA, without any further purification after precipitation. Genotypes of the one year post-mortem material and those of his son and his wife were obtained at the D1S80, HLA-DQ alpha, and STR loci. In all these systems, no exclusion was observed, with a combined probability of paternity of 0.9997. This demonstrates the reliability of the obtained results. The genetic typing of HUMTH01 in spongy bone from the XII-XIII Centuries Basque Country individuals was also performed. This will allow the genetic analysis of ancient bone remains and therefore, to carry out evolutionary population studies.
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PMID:Genetic typing with HUMTH01, HUMVWA31A and HUMFES/FPS short tandem repeat loci, D1S80 variable number tandem repeat locus and HLA-DQ alpha of recent and from XII-XIII centuries spongy bone. 858 43

Typing for HLA-B27 by serological methods is routinely performed using the microlymphocytotoxic test (MLCT). Since monoclonal antibodies (MAB) against HLA-B27 are available, flow cytometry (FC), which requires less time than the MLCT has been developed as an alternative technique. The aim of the present study was to check the accuracy and reliability of this method using different MAB against HLA-B27 in comparison to MLCT (using polyclonal antibodies against HLA-B27 and cross-reacting specificities [CRS]). FC was performed in 144 patients with HLA-B27-related rheumatic disorders (seronegative spondarthritides) using a special software package which requires corresponding calibration beads in order to achieve a standardized setup of the flow cytometer. MAB from the following producers were used: Becton & Dickinson (BD), Behringwerke (BE), One Lambda (OL), and Immunotech (IT). In addition to the critical limit of fluorescence intensity (FI) which indicates positivity if exceeded, provided by the software (but valid only for the MAB from BD), empirically twice the value of the STD calculated from the mean of the FI values of HLA-B27 positive patients was regarded a good cut off for the HLA-B27 positivity in FC measurements with the MAB used. Using a standard protocol including an incubation of whole EDTA-anticoagulated blood for 15 min with MAB against HLA-B27 (FITC-conjugated) and CD3 (PE-conjugated) and a lysis of erythrocytes, good discrimination between HLA-B27 positive and negative patients was obtained. Cross reactions with HLA-B27 positive patients occurred except when the MAB from OL was used. One false-negative result was found with OL's MAB (out of 22) and false-positive results occurred in HLA-B7+ patients when MAB from BD, BE, and IT were used. Unfortunately also 1 false-positive result (out of 57) was obtained in HLA-B7-, B27- patients with IT's MAB. Errors in the interpretation of the FC analysis might be avoided if more than one MAB (including those not cross reacting with HLA-B7) are used.
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PMID:Evaluation of four monoclonal antibodies against HLA-B27 for their reliability in HLA-B27 typing with flow cytometry (FC): comparison with the classic microlymphocytotoxic test (MLCT). 888 93

In chronic myeloid leukemia (CML) the classical 9;22 translocation results in a BCR-ABL fusion gene, which encodes chimeric BCR-ABL fusion 210 kD oncoproteins (p210BCR-ABL). The two main p210BCR-ABL fusion variants in CML, b2a2 and b3a2 are examples of well characterized antigens expressed by malignant cells. The possibility of an immunotherapeutic approach involving the fusion part of p210BCR-ABL in CML has previously been illustrated by observed peptide binding to major histocompatibility complex (MHC) class I alleles and by demonstrating the immunogenicity of p210BCR-ABL breakpoint peptides. In this report we show that in vitro immunization of human T cells with a 17 amino acid (aa) peptide representing the p210BCR-ABL fusion region resulted in peptide specific CD4+ T-cell lines designated P4, P6, and P7. HLA DR4 (DRB1*0401) restricted T-cell line P4 and several subsequently derived clones recognized HLA-DRB1*0401 and p210b3a2-mRNA expressing blasts from an allogeneic patient with CML in blast crisis. Recognition appeared DR expression-dependent. No responses were observed with DR4 positive p210BCR-ABL negative cells or with p210b3a2 leukemic cells with absent or insufficient expression of DR4. These observations indicate that oncoprotein p210b3a2 can be degraded and processed for presentation by MHC class II molecules at the surface of leukemic cells. The BCR-ABL fusion region is in all likelihood presented as peptides by HLA DR and thus capable to act as a distinctive tumor antigen to peptide specific CD4+ T cells.
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PMID:Recognition of BCR-ABL positive leukemic blasts by human CD4+ T cells elicited by primary in vitro immunization with a BCR-ABL breakpoint peptide. 889 19


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