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)

We report characterization of CD45 isoforms expressed by CD8+ lymphocytes in peripheral blood and in the graft of 40 kidney transplanted patients who underwent kidney biopsy on the basis of clinical signs suggesting rejection. Standard histological examination of the biopsy fragments and three-color cytofluorimetric analysis of lymphocytes extracted from the same fragments by mechanical and enzymatic treatment were performed simultaneously and compared to the peripheral blood lymphocytes. In 14/40 biopsies where lymphocyte extraction succeeded, the predominant subset was CD8 (CD4/CD8 mean ratio was 0.53). Almost all CD8+ cells were activated: among these CD8+ cells, 55 percent were HLA-DR+, and 68 percent CD45RO+, i.e. of a memory cell type with cytotoxic activity. This situation resembles the in vitro observation made during mitogenic stimulation of lymphocytes by phytohemagglutinin, OKT3 or CML ("culture mixte lymphocytaire"). Beside their evident interest for the diagnosis, these data could be useful for our understanding of the physiopathology of the rejection crisis.
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PMID:[Study of CD45 isoforms on T CD8 lymphocytes, in the peripheral blood and the graft in patients after kidney transplantation]. 129 62

Erythropoietin-receptor (EpR) expression on bone marrow cells from normal individuals and from patients with chronic myeloid leukemia (CML) was examined by multiparameter flow cytometry after stepwise amplified immunostaining with biotin-labeled Ep, streptavidin-conjugated R-phycoerythrin, and biotinylated monoclonal anti-R-phycoerythrin. This approach allowed the detection of EpR-positive cells in all bone marrow samples studied. Most of the EpR-positive cells in normal bone marrow were found to be CD45-dull, CD34-negative, transferrin-receptor-positive and glycophorin-A-intermediate to -positive. This phenotype is characteristic of relatively mature erythroid precursors, ie, colony-forming units-erythroid and erythroblasts recognizable by classic staining procedures. Approximately 5% of normal EpR-positive cells displayed an intermediate expression of CD45, suggesting that these represented precursors of the CD45-dull EpR-positive cells. Some EpR-positive cells in chronic myeloid leukemia (CML) bone marrow had a phenotype similar to the major EpR-positive phenotype in normal bone marrow, ie, CD34-negative and CD45-dull. However, there was a disproportionate increase in the relative number of EpR-positive/CD45-intermediate cells in CML bone marrow. Even more striking differences between normal individuals and CML patients were observed when EpR-expression on CD34-positive marrow cells was analyzed. Very few EpR-positive cells were found in the CD34-positive fraction of normal bone marrow, whereas a significant fraction of the CD34-positive marrow cells from five of five CML patients expressed readily detectable EpR. These findings suggest that control of EpR expression is perturbed in the neoplastic clone of cells present in patients with CML. This may be related to the inadequate output of mature red blood cells typical of CML patients and may also be part of a more generalized perturbation in expression and/or functional integrity of other growth factor receptors on CML cells.
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PMID:Increased erythropoietin-receptor expression on CD34-positive bone marrow cells from patients with chronic myeloid leukemia. 137 Jun 38

Pharmacologic differentiation of the promyelocytic leukemia HL60 is associated with an increase in cellular tyrosine phosphatase activity. We asked (a) if this increase might, at least in part, be due to changes in a transmembranous protein-tyrosine phosphatase, CD45; and (b) if CD45 changes similarly in other differentiating leukemias. Differentiation of HL60, several chronic myelogenous leukemias, a monocytic leukemia (THP-1), and a monoblastoid leukemia (U-937) could be induced by phorbol ester, 1,25-dihydroxy vitamin D3, dimethyl sulfoxide, or cyclic AMP analogues. This differentiation was associated with a marked increase in (a) total cellular tyrosine phosphatase activity (2-4-fold as measured by the ability to dephosphorylate a tyrosine-phosphorylated peptide); (b) CD45-specific tyrosine phosphatase activity (2-4-fold); (c) CD45 cell surface expression by flow cytometry (2-5-fold); (d) synthesis of both exon B-dependent M(r) 205,000 and exon ABC- M(r) 185,000 CD45 proteins, as revealed by immunoprecipitation with antisera specific for CD45 isoforms. Both isoforms have enhanced electrophoretic mobility when isolated from the differentiated cells. This enhanced mobility did not appear to be due to decreased stoichiometry of CD45 phosphorylation on serine/threonine residues. Interestingly, 12-O-tetradecanoylphorbol-13-acetate transiently reduced CD45 protein-tyrosine phosphatase activity in the chronic myelogenous leukemia cell RWLeu4 without altering the CD45 amount (as measured by cell surface immunofluorescence). Modulation of CD45 tyrosine phosphatase activity (and protein levels) may play a role in differentiation or in maintaining cells in a nonproliferative state or may represent a phenotypic marker of differentiation.
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PMID:Differentiation-induced changes in protein-tyrosine phosphatase activity and commensurate expression of CD45 in human leukemia cell lines. 153 52

Two bcr/abl fusion gene products with tyrosine kinase activity have been found in two phenotypes of Philadelphia chromosome (Ph1)-positive leukemia. P210bcr/abl (P210) is associated with Ph1-positive chronic myelogenous leukemia (CML), while P190bcr/abl is associated with Ph1-positive acute leukemia. We compared the susceptibility of 32Pi-labeled P210 from K-562 cells and P190 from MR-87 cells to protein tyrosine phosphatase (PTPase). PTPase, present in the lysate of mature granulocytes from CML patients as well as in the lysate of these cells from normal subjects, effectively dephosphorylated the CML-associated P210 and the acute leukemia associated P190. This PTPase activity was specifically inhibited by ZnCl2; it was not present in lymphocyte lysates, and was not inhibited by neutralization with anti-CD45 antibody. Since P210 and P190 were equally sensitive to the PTPase, the difference in leukemic phenotypes associated with the expression of these two tyrosine kinases cannot be explained by the differential dephosphorylation of P210 and P190.
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PMID:Two bcr/abl fusion gene products, P210bcr/abl and P190bcr/abl, are equally sensitive to the protein tyrosine phosphatase of mature granulocytes. 179 29

We describe for the first time a case report documenting a chronic myelogenous leukemia (CML) patient who developed a blast crisis of natural killer (NK) lymphocytes. Many of the blasts exhibited large granular lymphocytic (LGL) morphology. Single parameter immunophenotyping results determined that the granulated as well as the agranulated blast cells were NK lymphocytes (CD45, NKH1, CD2, LEU 17, and CD16 positive; CD3, CD8, and LEU 7 negative). Dual parameter flow cytometric testing also determined that some of the blasts expressed the CD11b and CD11c markers as reported for some types of NK lymphocytes. Approximately 10% of the cells were in the S phase of the cell cycle as determined by a modified Vindelov DNA content analysis test and may theoretically reflect some of those cells expressing CD11b and CD11c. The cells did not express in vitro NK lymphocyte functional activity against a K562 target and therefore similar to other reported cases of presumably immature NK lymphocytic leukemias. The NK lymphocyte blast crisis was successfully treated with vincristine and prednisone. The patient's disease eventually relapsed and transformed to a progenitor stem cell before she died (CD45, 13, CD38, and CD34 positive). The flow cytometric immunophenotyping results contributed significantly as an important adjunct in determining the appropriate diagnosis, helping to select the type of therapy, and monitoring the patient with this unusual type of blast crisis.
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PMID:Natural killer lymphocyte blast crisis of chronic myelogenous leukemia. 281 23

The mAb A6 was produced by immunization of mice with human PHA-stimulated PBMC. Immunoprecipitation studies and staining of cell lines transfected with individual leukocyte common antigen (LCA) isoforms showed that A6 recognizes a unique epitope strongly expressed on the lower MW isoform (p180) of LCA, but also weakly expressed on the p190 isoform coded by exon B and the p205 coded by exons A and B. The epitope recognized by A6 was carbohydrate-dependent in that it was neuraminidase-sensitive, but trypsin-resistant. A6 strained most TCR-alpha beta+ cells with differential intensities, subdividing them into a bright and dim population, and strongly stained all TCR-gamma delta+ cells. A6 did not stain CD19+ B cells nor CD56+ NK cells. Anti-CD45 mAb such as UCHL1 recognizing CD45RO have been used to define memory T cells. Depletion of PBMC subsets with A6 or UCHL1 mAb dramatically decreased proliferative responses to the recall antigens anti-CD3 mAb and alloantigen and enhanced their responses to PHA. A6, unlike UCHL1, also depleted alloreactive T cells that affect primary and secondary MLC and CML. Thus, A6 was shown to recognize the lower MW isoforms of LCA which are expressed on functional T cell subsets including memory, activated, and alloreactive T cells.
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PMID:A monoclonal antibody (A6) recognizing a unique epitope restricted to CD45RO and RB isoforms of the leukocyte common antigen family identifies functional T cell subsets. 752 74

The activity and mRNA expression of UDP-N-acetylglucosamine: beta-D mannoside beta-1,4-N-acetylglucosaminyl transferase III (GnT-III: EC 2.4.1.144) were investigated in hematological malignancies. GnT-III activity was elevated in patients with chronic myelogenous leukemia (CML) in blast crisis and patients with multiple myeloma (MM), as compared to normal healthy subjects and patients with other hematological malignancies including CML in chronic phase. The GnT-III transcript was the same size in leukemic cells from various hematological diseases and cell lines, while expression of the transcript was not found to correlate significantly with enzyme activity, implying that post-translational modification might regulate the activity of GnT-III. Southern-blot analysis showed no significant variation in the structure and position of the GnT-III genome, indicating that the gene is present as a single copy without isoforms. Furthermore, analyses by immunoprecipitation and Western blot revealed that high GnT-III activity in KU812 cell, a CML cell line, resulted in an increase in E4-PHA binding to CD45, a major surface glycoprotein of the leukocyte, indicating that more bisecting GlcNAc was added to CD45 catalyzed by elevated GnT-III.
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PMID:High expression of UDP-N-acetylglucosamine: beta-D mannoside beta-1,4-N-acetylglucosaminyltransferase III (GnT-III) in chronic myelogenous leukemia in blast crisis. 782 56

In an attempt to correlate the morphologic and immunophenotypic findings in extramedullary myeloid cell tumors (EMT), we studied 28 cases with a large panel of antibodies using paraffin section immunohistochemistry. A previous or concurrent diagnosis of acute myelogenous leukemia or chronic myelogenous leukemia was made in 25 cases. Six EMT were morphologically classified as well differentiated (WD-EMT), 17 as poorly differentiated (PD-EMT), and five as blastic EMT. The WD-EMT were easily recognized morphologically and displayed a relatively mature myeloid phenotype, with elastase, CD15, and CD68 positivity in all cases. On the other hand, the five blastic-EMT displayed no morphologic evidence of myeloid derivation, were completely negative for CD15, and were weakly positive for elastase in only one case. The PD-EMT, with a morphologic appearance that resembles large cell non-Hodgkin's lymphoma, variably expressed CD15 and elastase. CD68 and lysozyme were present in the majority of PD-EMT, with some variability, but were negative in most blastic-EMT. CD45 (LCA) was detected in 75% of all EMT and CD34 was positive in 36%; neither antigen was significantly associated with a specific morphology. CD30 reactivity was not evident in any case, but slight positive staining was seen with CD20 (L26) in one WD-EMT. CD43 (Leu 22) was the only antibody that was positive in 100% of cases; staining was always intense and widespread. Antimyeloperoxidase (MPO) was positive in all cases but two, both with a blastic morphology. We conclude that (a) an immunohistochemical panel including CD20, CD43, CD68, and MPO can successfully identify the vast majority (96%) of EMT in paraffin sections, and (b) there is an association between morphology and phenotype in these lesions.
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PMID:Extramedullary myeloid cell tumors. An immunohistochemical and morphologic study of 28 cases. 837 41

The membrane expression of CD45RA and CD45RO on fresh leukaemic cells taken from 529 cases of acute haemopoietic malignancies, including 117 B-origin acute lymphoblastic leukaemia (B-origin ALL), 37 T-origin acute lymphoblastic leukaemia (T-origin ALL0, 297 de novo acute myeloid leukaemia (AML), 42 refractory anaemia with excess of blasts in transformation (RAEB-T) and 36 myeloid blastic phase of chronic myelogenous leukaemia (CML-BP-my), was analysed. B-origin ALLs were characterized by the lack of the RO isoform along with the consistent presence of RA. Conversely, a differential expression of the two isoforms was detected in different subsets of T-origin ALL, in that T-stem cell leukaemias (T-SCL: CD7+, CD4-, CD8-, CD1-) preferentially expressed CD45RA whereas conventional T-acute lymphoblastic leukaemias (T-ALL: CD7+, CD4+ and/or CD8+ and/or CD1+) were consistently marked by CD45RO. Within myeloid malignancies, most of AMLs displayed CD45RA, while a substantial group of CML-BP-my preferentially exhibited CD45RO. As a general rule, a reciprocal exclusion of the two isoforms was observed in AML as well as in ALL. Nevertheless, a frequent coexpression of CD45RA and CD45RO was observed in CD14+ AML. In vitro treatment with all-trans retinoic acid (ATRA) was able to promote a switch from CD45RA to CD45RO expression in 27 de novo AML, independently from morphological subtyping. To our knowledge, this is the first report on CD45 isoform expression in a large series of patients with acute leukaemia. The knowledge of the differential expression of CD45RA and CD45RO can ameliorate our classificative approach to haematological malignancies, as well as disclose new multiple overlap points between normal and leukaemic cell differentiation.
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PMID:Expression of the leucocyte common antigen (LCA, CD45) isoforms RA and RO in acute haematological malignancies: possible relevance in the definition of new overlap points between normal and leukaemic haemopoiesis. 854 36

In our study we used for definition of leukemia/lymphoma cells a new parameter which allows the enumeration of mean fluorescence intensity expressed by the number of antigen molecules per cell. Quantitative immunofluorescence using calibration microbeads was performed in 36 patients with different acute and chronic lymphoid and myeloid leukemia and in 19 healthy volunteers. We showed that quantitative immunophenotyping allowed the definition of aberrant marker densities on neoplastic cells. We demonstrated under- and overexpression of CD8 marker in CD3/CD4/CD8 complex in T acute lymphatic leukemia and T non-Hodgkin's lymphoma and T leukemia of large granular lymphocytes as compared to normal counterparts. We pointed out that certain antigens (e. g. CD10, CD4, CD24) were expressed at different levels on different cell subsets (CD10 in early B-acute lymphatic leukemia and coexpressed in T-acute lymphatic leukemia, CD4 on T cells and monocytes, CD24 on B cells and granulocytes in chronic myeloid leukemia). We showed that quantitative immune fluorescence could provide new data contributing to a more precise definition of cell differentiation. We documented the significant difference between antigen density of early and late markers in B-cell and myeloid malignancies. Further, we demonstrated that quantitative immune phenotyping could help in determination of exact definition of pathologic clone in morphologically immature leukemia population and showed that parameters of this method are also convenient for cytoplasmic marker evaluation. In our study we were able to demonstrate that CD45 quantitative expression appeared to be a more informative parameter than its percentage of antigen-positive cells as a measure of antigen expression only and we pointed out that low and high CD45 densities enabled to differentiate between pathological clone and residual healthy population in examined sample. We showed that quantitative immune phenotyping could be another important parameter for definition of leukemia phenotype suitable for detection of minimal residual disease.
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PMID:Quantitative immunocytofluorometry--new parameters for the definition of leukemia cells. 960 6


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