UMLS:C0023473 - FACTA Search

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Query: UMLS:C0023473 (chronic myeloid leukemia)
18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two patients with chronic myelocytic leukemia (CML) mixed crisis and one with Philadelphia-chromosome-positive (Ph1 +) acute lymphoblastic leukemia (ALL) with cross-lineage nature had a considerable number of granulocytes with monoclonally rearranged immunogenotype. The gene configurations of immunoglobulin heavy chain (IgH), T-cell receptor beta chain (TCR beta), and gamma chain (TCR gamma) in the granulocytic cells were identical to those in the blasts, indicating that both the blasts and the granulocytes were derived from common leukemic progenitors with the IgH gene rearrangements. In a colony assay of cells from in the Ph1 + ALL patient, the leukemic cells showed the potential to differentiate into granulocytes in the presence of either granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte-CSF (G-CSF). Interleukin 7 (IL-7) exerted synergistic effects on colony and cluster formation in cultures with these cytokines. Further, IL-3, GM-CSF, and G-CSF receptor gene expression was found in the leukemic cells. Our findings indicate that the Ph1 + common progenitors in these three patients preserved the potential for granulocytic differentiation even after the occurrence of the Ig (and TCR) gene rearrangements as the first genomic event in lymphocyte differentiation. The phenomenon of cross-lineage in leukemic cells, at least in Ph1 + leukemia, can be considered to demonstrate the potential of leukemic progenitors to differentiate in multiple directions.
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PMID:A granulocytic population with rearranged immunogenotype in chronic myelocytic leukemia blast crisis and Philadelphia-chromosome-positive acute leukemia with cross-lineage nature. 838 Nov 95

We have analyzed the immunological and genomic characteristics of the lymphoid blast cells present in secondary lymphoid leukemias following either a previous chronic myelogenous leukemia (CML) or myelodysplastic syndrome (MDS). Twenty-one of 107 secondary leukemias analyzed displayed a lymphoid phenotype (15 after a CML and 6 after a MDS). Most of the lymphoid blast crises of CML (73%) correspond to pure lymphoid transformation, all of them having a common acute lymphoblastic leukemia (ALL) phenotype (CD10+). By contrast, in all MDS cases, lymphoid blast cells coexisted with another myeloid component (hybrid leukemias) and showed an early B phenotype. IgH and TCR-gamma gene rearrangements were detected in the CML-lymphoid blast crisis (86% of cases) more frequently than in the MDS transformations (33%). The TCR-beta gene was in germ line configuration in all cases while TCR-delta gene rearrangements were detected in four cases, all of them corresponding to a previous diagnosis of CML. These results show the existence of both immunophenotypic and genomic differences between the lymphoid transformations of either CML or MDS, which could reflect differences at the stage of maturation of the target cell in these transformations.
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PMID:Acute lymphoid leukemias following either a previous chronic myelogenous leukemia or myelodysplastic syndrome: phenotypic and genomic differences. 804 98

Monoclonal antibodies to CD3 have been shown to activate T cells in vivo and in vitro but have also been shown to render T cells anergic in vitro. In this study G4.18, a mouse IgG3 mAb, was produced that appeared to recognize CD3 by its binding to all peripheral T cells, including a population not recognized by mAb to TCR-alpha/beta that was presumed to be TCR-gamma/delta cells. It precipitated molecules in the 24-26 kd region consistent with the CD3 complex as well as molecules approximately 45 and approximately 49 kd that corresponded to TCR alpha and beta chains and a 92-kd complex. Incubating T cells for 24 hr with saturating concentrations of G4.18 caused modulation of the TCR complex. In vitro, it activated T cells but only if prebound to plastic. In solution it inhibited MLC and CML, but not PHA or Con A activation. In vivo, G4.18 was not toxic even in high doses, and this was thought to be due to the inability of this mAb to activate T cells in vitro because the rat lacks Fc receptors for mouse IgG3. Therapy with G4.18 resulted in transient modulation of TCR/CD3 on T cells and depletion of these cells from blood. G4.18 had no depleting effects by lymph node or spleen cells but caused marked, transient thymic involution. Therapy with G4.18 also induced indefinite survival (> 100 days) of PVG (RTIc) heart grafts but not skin grafts in DA (RTIa) hosts. These hosts with long-surviving cardiac transplants, when grafted from PVG skin, accepted these grafts but rejected third-party skin in first-set. Thus G4.18 was shown to induce long-term specific tolerance to an organ allograft.
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PMID:Induction of long-term specific tolerance to allografts in rats by therapy with an anti-CD3-like monoclonal antibody. 845 60

In December 1993, a 76-year-old Japanese male presented with general fatigue. Peripheral blood (PB) examination indicated marked leukocytosis (WBC count, 19.8 x 10(4)/microliter; leukemic blast differential, 89.5%). Leukemic blasts were positive for CD33, and negative for lymphoid antigens, with 2% of the blasts being positive for myeloperoxidase staining. On admission, chromosome analysis of leukemic cells in PB showed 45, X,-Y, t (9;22) [12/15]/46, XY, t (9;22) [3/15]. Southern blot analysis of the DNA from PB showed a rearrangement at the M-BCR region and germline configurations of both TCR beta and IgH chain genes. The patient was diagnosed as Philadelphia-positive chronic myelogenous leukemia (CML) in blast crisis. We commenced treatment with daunorubicin (DNR; 20 mg/day x 1 IV) and daily prednisolone (PSL; 60 mg/day PO). Leukemic blasts disappeared rapidly from PB, while the promyelocytes showed a transient increase, peaked 7 days after the start of therapy, and then disappeared. Myelocytes and metamyelocytes also showed transient increases. Without a period of severe myelosuppression, the patient reverted to the chronic phase of CML and karyotypic analysis of bone marrow cells showed 45, X,-Y, t (9;22) [33/35]/46, XY, [2/35]. Consolidation chemotherapy with DNR and BHAC was started, but the patient's condition deteriorated due to bacterial infection and he died of hepatic failure on March 1994. In this case, reversion to the chronic phase of CML in blast crisis may be accomplished by the cytodifferentiating effects of small-dose DNR and oral PSL to the leukemic blasts.
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PMID:[Reversion to chronic phase of chronic myelogenous leukemia in blast crisis with small-dose daunorubicin and oral prednisolone]. 858 71

Liver infiltrating lymphocytes (LIL) were isolated from HCV-positive (+) and HCV-negative (-) end-stage livers. Phenotypic analysis and functional studies using proliferative and lymphocytotoxic assays were performed with the isolated LIL. Two CD3+ lymphocyte populations were found in LIL using FITC anti-CD3 monoclonal antibodies (mAb). One was a bright fluorescence intensity population (as in PBL), and the other dim. We calculated the number of FITC-anti-CD3 mAbs bound per lymphocyte on PBL and LIL and found 80,040 +/- 4628 and 39,615 +/- 3932, respectively. Therefore, HCV+ and HCV- patient PBL contained approximately twice the number of CD3 molecules per cell than patient CD3+ LIL. LIL also contained approximately a threefold higher concentration of TCR alpha beta +, CD4-CD8-, and CD56,16 (NK) cells than the patient PBL. Thus, a major subset of LIL is phenotypically similar to mouse NK1.1+ "intermediate" T cells. LIL freshly isolated from HCV+ livers exhibited weak CTL activity against EBV- or Con A-transformed lymphoblast targets infected with vaccinia-HCV recombinant virus (rHCV) or primary hepatocyte cultured cells. However, after in vitro coculture of LIL with rHCV, these cells developed a strong cytotoxicity for the above targets. In contrast, LIL from HCV- livers were not cytotoxic against the same targets. Histochemical studies (in situ) demonstrated that these hepatocytes express CD95, and stains demonstrated apoptosis. The HCV+ hepatocytes also express class I MHC molecules and ICAM-1. The addition of mAb specific for these adhesion molecules inhibited CML activity. Short-term cultured hepatocytes (targets) from HCV+ and HCV- patients produced low levels of cytokines IL-1 beta, IL-2, IL-6, TNF alpha, and IFN-gamma but a high level of IL-8. It is speculated that LIL expressing reduced numbers of CD3 molecules may even function as immune regulators as proposed for intermediate T cells in mice.
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PMID:The immune reactivity role of HCV-induced liver infiltrating lymphocytes in hepatocellular damage. 908 90

The results of studies from a regional cancer cytogenetics diagnostic service are reported. In a 10-year period, 1,143 marrow samples from patients with newly diagnosed leukemia and myelodysplastic syndrome were referred. Successful studies were completed on 992 cases (87%). Among all referred cases, the rates of detection of cytogenetically abnormal clones were 95% for chronic myelogenous leukemia (CML), 54% for acute lymphoblastic leukemia (ALL), 51% for acute myeloid leukemia (ANLL), and 43% for myelodysplastic syndrome (MDS). Of 169 cases of CML studied, 90.5% bore the standard Philadelphia chromosome (Ph), 3.55% had an unusual Ph, and 5.33% were Ph-negative. Among the 59 cases of cytogenetically abnormal MDS, common abnormalities observed were trisomy 8 and changes resulting in loss of material from the long arm of chromosomes 5 and 7, and 20q-. Of the 168 abnormal ANLL, there was a strikingly non-random pattern of aneuploidy, with monosomy 7 and trisomy 8 predominating. Common structural changes observed were changes resulting in loss of material from the long arm of chromosomes 5 and 7, trisomy 8, rearrangements of 11q23, t(15;17), t(8;21), rearrangements of 12q13 and 3q, inversion 16, trisomy 11, Ph, trisomy 21, t(6;9) and t(1;22). The differences between adult and pediatric findings were minor, with the exception of chromosome 5 abnormalities, which were common among adults with ANLL but rare in the pediatric cases. There were 273 ALLs with abnormal cytogenetic findings. There was preferential gain of chromosomes 21, X, 14, 6, 4, 18, 17, and 10 (in decreasing order of frequency) in leukemic clones. Of the 193 ALLs with structural changes, many fell into-well-defined categories with established correlations to FAB subtypes. Common changes in ALL were rearrangements of 9p, 12p, 6q, TCR loci, 11q23, Ig loci, and 8q24, and duplication of 1q, Ph, i(17q), t(1;19), i(9q) and dic(9;12). The detailed documentation of the cytogenetic findings in this relatively large, single-institution study will likely facilitate the further characterization of rare, primary cytogenetic changes associated with leukemias and MDS. From a managed health care perspective, regional cancer cytogenetic services may be cost-effective alternatives to single-institution laboratories.
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PMID:Regional cancer cytogenetics: a report on 1,143 diagnostic cases. 920 73

The role of T lymphocytes in the control of chronic myeloid leukemia (CML) after bone marrow transplantations has been clearly shown. This effect closely correlates with graft-versus-host disease (GVHD). A specific graft-versus-leukemia (GVL) effect separate from GVHD has been postulated but has been difficult to show. One possible target for specific GVL activity is the bcr-abl fusion protein characteristic of CML. We have investigated the use of normal peptide-pulsed dendritic cells for the generation of cytotoxic, bcr-abl-specific T cells from normal donors. T cells (CD3+, CD8+, TCR alpha beta+, and NK receptor-negative) generated from a normal donor (HLA A24, B52, B59, Cw1) after stimulation with autologous dendritic cells, primed with a 16 mer peptide spanning the b3a2 breakpoint of bcr-abl, lysed CML cells from the peripheral blood of seven patients with CML with the b3a2 breakpoint. CML cells from four patients with only the b2a2 breakpoint were not lysed. Phytohemagglutinin (PHA) blasts derived from peripheral blood of patients with CML were not lysed, suggesting that cytotoxicity was not due to alloreactivity. Blocking experiments with anti-HLA-A,B,C indicated that cytotoxicity was dependent on recognition of major histocompatibility complex (MHC) class I molecules, although cytotoxicity was not MHC-restricted because not all patients shared HLA types with the T-cell donor. Specificity for bcr-abl and absence of alloreactivity was confirmed by the presence of lytic activity against autologous and allogeneic class I HLA-A matched monocytes pulsed with the 16 mer bcr-abl fusion peptide, but not against unpulsed monocytes or monocytes pulsed with other peptides. These results show that bcr-abl-specific T cells with marked cytotoxic activity against CML cells can be generated and amplified from normal donor peripheral blood. Recognition of HLA molecules is essential for cytotoxicity but strict HLA identity is not required.
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PMID:Dendritic cells stimulate the expansion of bcr-abl specific CD8+ T cells with cytotoxic activity against leukemic cells from patients with chronic myeloid leukemia. 944 59

The pathogenic mechanisms of immunosuppression leading to susceptibility of Mycobacterium tuberculosis (MT) infection in chronic myelocytic leukemia (CML) are not clear. To address this issue, we measured the proliferative response, variation of T cell subpopulations (CD4+, CD8+, TCR-V delta 2 and TCR-V beta 8 T cells) and the cytokine profile (IL-1 beta, IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma) after MT stimulation of peripheral blood mononuclear cells (PBMC) in a patient with concomitant CML and active pulmonary tuberculosis. The results were compared to four patients with active pulmonary tuberculosis and no other coexistent diseases. The immunologic response to phytohemagglutinin (PHA) was also evaluated. In contrast to controls, the CML PBMC failed to proliferate in response to MT antigens. Mycobacterium-reactive CD4+, V delta 2 and V beta 8 T cells did not expand after MT stimulation of the CML PBMC. In MT antigens-stimulated cultures from the CML patient, IL-2 was not produced and mild reduction of IL-1 beta and INF-gamma were observed. In contrast, IL-10 was markedly elevated in these cultures. Similarly, PHA-stimulated PBMC from the CML patient showed no expansion of CD4+ and CD8+. T cells. In these cell cultures, INF-gamma concentration in supernatants was decreased and IL-10 was significantly elevated. This study suggests that patients with CML may present a profound immunosuppression of essential cellular and molecular immune effectors, a scenario which might contribute to the development of active tuberculosis. These findings further support the need of establishing immunotherapeutic modalities with potential value for myeloproliferative disorders.
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PMID:Abnormal immunological response to Mycobacterium tuberculosis antigens in a patient with chronic myelocytic leukemia and active tuberculosis. 1002 42

Careful longitudinal studies of the lymphoid cell recovery after stem cell transplantation with other than HLA-identical sibling donors illustrated the prolonged T- and B-cellular immunodeficiency post-SCT, whereas NK-cell recovery was fast. Only low numbers of CD45RO memory T-cells, with a restricted TCR-repertoire, are present in the first 6 months post-SCT. The consequence is an increased risk of viral infections and possibly of leukemia relapse. The latter complication can be prevented by enhancing the anti-leukemic immune reactivity shortly after SCT. Different technical approaches were presented, the majority of them still being in the pre-clinical phase. NK-cell reactivity based on KIR-epitope mismatches between donor and recipient are promising for AML- and CML-, not for ALL-patients. The ALL-blasts may be killed by an antibody-dependent cellular cytotoxicity, using anti-CD19 antibodies, as was shown to be effective in vitro. Also the generation of leukemia-specific CTL's, making use of differences in minor histocompatibility antigens between donor and recipient, is now operational and may be a highly effective approach in a number of leukemic graft recipients.
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PMID:Immune recovery and immunotherapy after stem cell transplantation in children. 1157 27

To investigate the T cell distribution characters of TCR Vbeta repertoire in Ph(+) and Ph(-) CML. The 24 subfamilies of the TCR Vbeta genes were amplified in peripheral blood T cells from 13 patients with CML (Ph+ b3a2, 5 cases; Ph+ b2a2, 5 cases; Ph(-), 3 cases) by RT-PCR, to analyze the usage of Vbeta subfamilies in different CML patients. The results showed that the expression pattern of Vbeta repertoire was different in normal individuals and in patients with CML which only have part of Vbeta subfamily T cells. 4 - 16 (mean 10.2) Vbeta subfamily T cells were detected in the Ph+ b3a2 CML, 8 - 11 (mean 8.8) Vbeta subfamily T cells in the Ph(+) b2a2 CML and 5 - 6 (mean 5.7) in Ph(-) CML. Moreover, the expression of Vbeta subfamily T cells was different among these three types CML.Vbeta10 and Vbeta16 were detected in the all cases with Ph(+) b3a2 and Ph(+) b2a2 CML, whereas Vbeta9 and Vbeta22 could be found in the most cases with Ph(+) b3a2 CML or Vbeta24 and Vbeta8 in Ph(+) b2a2 CML. In patients with Ph(-) CML, Vbeta24 were detected in all samples, and Vbeta9, Vbeta10, Vbeta13 and Vbeta22 were found in the most cases. The results suggest that skew distribution of TCR Vbeta subfamily T cells was existed in peripheral blood of Ph(+) and Ph(-) CML patients. The selected usage of TCR Vbeta is different in various types of CML patients. It may relate to difference of CML cells associated antigen and individual special immunity reaction.
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PMID:[The distribution feature of TCR Vbeta repertoire in peripheral blood T cells from patients with Ph(+) and Ph(-) CML]. 1251 13

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