Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of HLA antigens in the generation of cytotoxic cells in CML has been investigated. Cytotoxic effector cells were generated in MLC among HLA-A or HLA-A and HLA-B disparate, HLA-D identical siblings, and among HLA-A and HLA-B disparate, MLC identical (%RR less than or equal to 2 3.6) unrelated individual. The data indicate that HLA-D differences and poliferative MLC responses as measured by 3H-thymidine incorporation are not requisite for the in vitro generation of cytotoxic cells and suggest the existence of a CML-S locus (loci) distinct from HLA-A, HLA-B and HLA-D. The degree of cytotoxicity generated in a proliferative versus a "nonproliferative" MLC was comparable. In addition, these studies demonstrate that antigens other than the currently definable HLA-A, HLA-B, HLA-C, and HLA-D can serve as target determinants in cell-mediated lympholysis.
 ...
PMID:The genetics of cell-mediated lympholysis. 6 6

The aim of our study was to define target determinants other than those coded for by the classical HLA-A, -B, -C or -D loci which were responsible for killing in CML. In one of the families studied, strong evidence was found for the existence of a determinant coded for within the HLA region. CML was restricted to targets carrying the classical HLA-Bw35 and Cw4 determinants but the targets were neither HLA-Bw35 nor Cw4 themselves. We therefore concluded that this new HLA determinant was either the product of a new locus closely associated with HLA-B or that it was a product of the classical HLA-B locus which has not been recognized by serology.
 ...
PMID:HLA restriction of non-HLA--A, --B, --C and --D cell mediated lympholysis (CML). 6 23

It now appears unequivocal that three markers exist in a linkage group in chromosome 6 of man: HLA-A, HLA-B and PGM3 (Fig. 1.) Tentatively, two other HLA loci and one Ir gene have been mapped close to HLA-B. The probable map order is HLA-A - HLA-C - HLA-B - HLA-D - Ir. The biological functions of these loci are unknown. However, HLA-A, B and C are important in allograft rejection. Other closely linked loci (HDR, CML) appear to be important in the first events of the allograft rejection (first set) and in generation of killer cells. HLA-D might be important in cellular recognition and graft-versus-host reactions (matching at HLA-D decreases the incidence and severity of graft-versus-host disease), and the Ir genes in the defense against infections. HLA-B and HLA-D loci are important markers in studies of disease susceptibility. HLA-B locus antigens HLA-B27 and HLA-B8 are frequently associated with arthritic or autoimmune disorders. HLA-D determinants have been found in association with multiple sclerosis and C2 deficiency (HLA-DW2); juvenile diabetes and Addison's disease (HLA-DW3) and adult type of rheumatoid arthritis (HLA-DW4).
 ...
PMID:Immunogenetic aspects of allotransplantation. 13 74

The functions of the genes included in the HLA complex have been studied mainly through the allogenic response, in vitro and in vivo. The sequence of this response was established thanks to primary and secondary MLC and CML. It appears that at least two clones of T lymphocytes are involved, the first in the non-self recognition through HLA-D differences, and the second in immunization against the HLA-A and B incompatibilities. Many associations between HLA and diseases have been found. They can be classified in three categories according to their associations with HLA-B, D, or with another gene of the complex. They are true experiments of nature which will give clues to the physiological functions of the HLA complex genes.
 ...
PMID:[Physiology and pathology of the HLA complex (author's transl)]. 30 Jun 3

Investigating HLA-A, HLA-B, HLA-C, and HLA-DR antigens, MLR, CML, and PLT reactivity in two unrelated persons it was found that despite their HLA-D/DR identity cytotoxic T lymphocytes (CTL) could be induced in the CML assay. The HLA-DP antigens proved to provide the necessary proliferative impetus for the generation of CTL.
 ...
PMID:HLA-D/DR identity results in a positive CML reaction. 265 91

The human leucocyte antigens (HLA)-Bw4/Bw6 antigens detected serologically are "public" determinants located in the HLA-B molecule. They do not generate cytotoxic T lymphocytes (CTLs) in primary allogeneic cultures (mixed lymphocyte antigens) and secondary (primed lymphocyte typing) cultures indicate that they do not behave like normal HLA "private" cell-mediated lympholysis determinants. Therefore, the contribution of the 79-83 (alpha 1) residues in the generation of the epitopes Bw4/Bw6 does not seem to be critical for the examination by T cell receptor in allogeneic CML. The different overlapping patterns of the serological and CTL examinations are discussed, based on the structure of HLA class I antigens.
 ...
PMID:The "public" determinants HLA-Bw4/Bw6 do not generate cytotoxic T lymphocytes (CTLs). 279 Sep 69

Previous studies have shown that lymphocytes from renal allografted patients with a good functioning graft display donor-specific cell-mediated lympholysis nonreactivity (CML-NR) in vitro. To define whether the HLA system influences the occurrence of the CML-NR, immunogenetic studies were carried out. Posttransplant lymphocytes derived from CML-NR patients were stimulated in vitro with lymphocytes from unrelated healthy blood donors, who were selected for the presence or absence of kidney donor-specific HLA antigens. The presentation of kidney donor-specific HLA-B (and -C) antigens on the lymphocytes of unrelated blood donors resulted in cytolytic nonresponsiveness, whereas presentation of the kidney donor-specific HLA-A locus antigens on lymphocytes of the unrelated blood donors revealed no cytolytic nonresponsiveness. The results, as displayed by posttransplant lymphocytes of renal allografted patients, demonstrate that the kidney donor HLA-B (and -C) antigens are responsible for the in vitro-observed, donor-specific CML-NR. Consequently, presentation of cells from panel members matched to the kidney donor at the HLA-B locus suppresses the response towards HLA-A locus antigens. The in vitro-observed cytolytic nonresponsiveness appeared not to be due to an absence of specific cytotoxic T lymphocytes, because the nonresponsiveness can be abrogated by addition of exogenous IL 2.
 ...
PMID:HLA regulates postrenal transplant CML nonreactivity. 390 Feb 3

Some CTLs recognize HLA-structures in a different way than antibodies, i.e. they may identify other epitopes than antibodies or may define genetically distinct structures. From population studies, in vitro educated CTLs were selected giving rise to significant lysis on PHA-lymphoblasts in the absence of the sharing of HLA-A, B, (C) determinants between stimulator and target lymphocytes. Based on pair-wise correlations these CTLs form 3 clusters, identifying structures associated to HLA-markers. Subsequent testing in 14 complete families of greater than or equal to 4 children allowed the observations: (1) CML-traits assigned on the basis of single CTLs often segregated in a non-mendelian way or independent of HLA. (2) Assignment made on the basis of CTL-clusters segregated with HLA. (3) in 2 informative HLA-B/D, DR recombinant families, CML-traits segregated with HLA-B. (4) No haplotype could be assigned more than one CML-trait.
 ...
PMID:Typing by cytotoxic lymphocytes. Genetics of HLA-non-A, B, C determinants - family studies. 646 Oct 89

D cells are lymphocytes bearing both receptors for the third complement component and the ability to form spontaneous rosettes with SRBC. We report the case of a patient with a D-cell chronic lymphatic leukemia who presented a long evolution without treatment and whose leukemic cell characteristics have been extensively studied. Cytogenetic analysis showed numerous karyotypic abnormalities among leukemic cells; all metaphases were hypodiploid and arranged in four different clones; seven marker chromosomes were present. The cells were found to bear human T-cell specific antigen, the T helper/inducer phenotype, HLA-A and HLA-B determinants, but no HLA-DR antigens. They displayed a high proliferative response to PHA and Con A, no response to PWM stimulation, and possibly the capacity of allogeneic stimulation in the mixed lymphocyte culture system. Assays for cell-mediated cytotoxicity in the CML system, and for K and NK activities were negative.
 ...
PMID:Membrane markers, karyotypic abnormalities, ultrastructure and functional properties of lymphocytes in a case of 'D-cell' chronic lymphatic leukemia. 671 63

The diminished response to secondary stimulation of human lymphocytes primed in bi-directional (BD) mixed lymphocyte culture (MLC) has been demonstrated to be due to cytotoxic destruction of the responder cells by the numerically superior allogeneic stimulating cell population. This phenomenon is called Functional Cell Mediated Lympholysis (F-CML). Matching for HLA-A and B, HLA-DR or for MLC non-responsiveness (HLA-D) in unrelated pairs does not ablate F-CML, indicating that none of these loci serve as the exclusive target for this activity. One locus appears to be centromeric from HLA-A in an A/B recombinant family and a B/D recombinant family demonstrates a target centromeric from HLA-B. A special family with homozygous for HLA-A, B and D provided evidence for an additional locus other than HLA-A, B or D. Thus, genetic studies indicate that at least one target antigen of F-CML may be coded for by a locus that is centromeric from HLA-B and which may be distinct from HLA-D or DR.
 ...
PMID:Functional cell mediated lympholysis: II. Genetics. 694 37


1 2 Next >>