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)

Chronic myelogenous leukemia (CML) is characterized by a translocation involving the c-abl protein-tyrosine kinase gene. A chimeric mRNA is formed containing sequences from a chromosome 22 gene (bcr) at its 5' end and all but the variable exon 1 of c-abl sequence. The product of this mRNA, p210bcr-abl, has constitutively high protein-tyrosine kinase activity. We examined K562 cells and other lines established from CML patients for the presence of phosphotyrosine (P-Tyr)-containing proteins which might be p210bcr-abl substrates. Two-dimensional gel separation of 32P-labeled proteins followed by phosphoamino acid analysis of 25 phosphoproteins, which comprised the major alkali-stable phosphoproteins, indicated that three related proteins of 41 kDa are the most prominent P-Tyr-containing proteins detected by this method. The 41-kDa phosphoproteins are found in two other CML lines that we examined but not in lines of similar lineage isolated from patients with distinct leukemic disease. A protein that comigrates with the major form of pp41 (pp41A) and contains P-Tyr is also found in murine fibroblasts and B-lymphoid cells transformed by Abelson murine leukemia virus, which encodes the v-abl protein, and in platelet-derived growth factor-treated fibroblasts, in which it has been described previously. We analyzed three pairs of Epstein-Barr virus-immortalized B-cell lines from individual CML patients and found that only the lines in which active p210bcr-abl was present contained detectable pp41. We also performed immunoblotting with anti-P-Tyr antibodies on the same CML cell lines and detected at least four other putative substrates of p210bcr-abl, which were undetected with use of the two-dimensional gel technique.
 ...
PMID:A 41-kilodalton protein is a potential substrate for the p210bcr-abl protein-tyrosine kinase in chronic myelogenous leukemia cells. 154 12

In addition to the 85-95 kD CD44 species found on most hemopoietic cell types, the human myelomonocytic cell line KG1a expresses proteins of approximately 115 kD and 130 kD that react with monoclonal antibodies belonging to CD44. The possibility that these higher molecular weight species may represent novel CD44 isoforms containing additional protein sequence was investigated. CD44 cDNA clones were isolated from a plasmid-based expression library prepared from KG1a mRNA. One of the three clones obtained (clone 2.3) was found to encode a CD44 molecule of approximately 130 kD in transfected COS cells. Sequences analysis indicated that the molecule encoded by this cDNA clone, designated CD44R1, was essentially identical to CD44 except for the presence of an additional 132 amino acids inserted into the extracellular domain. This inserted region is rich in serine and threonine residues that may serve as sites of O-linked glycosylation, and contains a potential site of N-linked glycosylation and a potential site of chondroitin sulphate attachment. PCR analysis using primers that flank the inserted region present within CD44R1 identified an additional CD44 isoform, designated CD44R2, that contains only the last 69 amino acids present within the unique region of CD44R1. Peripheral blood mononuclear cells and granulocytes from normal individuals and patients with chronic myelogenous leukemia, polycythemia vera, or acute myelomonocytic leukemia, express both CD44R1 and CD44R2. In contrast, CD44R1 and CD44R2 appear to be differentially expressed in various CD44-positive cell lines. Thus KG1a, and the Epstein-Barr Virus-transformed B cell lines WalkDR4 and Way-1 express both CD44 and the CD44 isoforms CD44R1 and CD44R2, while the myeloid cell lines HL60 and U937 express high levels of CD44, but only very low levels of CD44R1 and CD44R2. The CD44-negative cell lines DHL-4, DHL-10, Jurkat, and K562 are also negative for CD44R1 and CD44R2.
 ...
PMID:Molecular cloning of CD44R1 and CD44R2, two novel isoforms of the human CD44 lymphocyte "homing" receptor expressed by hemopoietic cells. 205 74

A cell line secreting a human monoclonal antibody was established by Epstein-Barr virus transforming B cells derived from an enlarged cervical lymph node excised from a patient bearing a carotid body tumor. The reactivity of the monoclonal antibody, designated as mNISP, was tested on various cells and cell lines. An antigen defined by the mNISP was expressed on some Burkitt's lymphoma cell lines and on a non-T non-B acute lymphoblastic leukemia cell line. Furthermore, this antigen was expressed on leukemic cells from 2 of 8 patients with chronic myelocytic leukemia, 2 of 10 patients with acute myeloblastic leukemia, one of 13 patients with acute lymphoblastic leukemia, and two patients with adult T cell leukemia, but it was not expressed on normal T, B and adherent (macrophage) cells. In addition, mNISP reacted with T cells obtained from human T-cell leukemia virus type I carriers. We found that the antigen defined by mNISP was distinct from any previously reported antigen in terms of its pattern of cellular expression and molecular weight, suggesting that mNISP recognizes a new antigen expressed on some lymphoid cells.
 ...
PMID:Production and characterization of a human monoclonal antibody recognizing a new antigen expressed on some lymphoid cells. 213 42

A transcriptional enhancer has been mapped to a region 5.5 kilobases 3' of the C beta 2 gene in the human T-cell receptor (TCR) beta-chain locus. Transient transfections allowed localization of enhancer activity to a 480-base-pair HincII-XbaI restriction enzyme fragment. The TCR beta enhancer was active on both the minimal simian virus 40 promoter and a TCR beta variable gene promoter in both TCR alpha/beta + and TCR gamma/delta + T cells. It displayed significantly less activity in Epstein-Barr virus-transformed B cells and K562 chronic myelogenous leukemia cells and no activity in HeLa fibroblasts. DNA sequence analysis revealed that the enhancer contains a consensus immunoglobulin kappa E2 motif, as well as an AP-1-binding site and a cyclic AMP response element. DNase I footprint analyses using Jurkat T-cell nuclear extracts allowed the identification of five nuclear protein-binding sites, T beta 1 to T beta 5, within the enhancer element. Deletion and in vitro mutagenesis studies demonstrated that the T beta 2- and T beta 3- and T beta 4-binding sites are each required for full transcriptional enhancer activity. In contrast, deletion of the T beta 1- and T beta 5-binding sites had essentially no effect on enhancer function. Electrophoretic mobility shift assays demonstrated that TCR alpha/beta + and TCR gamma/delta + T cells expressed T beta 2-, T beta 3-, and T beta 4-binding activities. In contrast, non-T-cell lines, in which the enhancer was inactive, each lacked expression of at least one of these binding activities. TCR alpha and beta gene expression may be regulated by a common set of T-cell nuclear proteins in that the T beta 2 element binding a set of cyclic AMP response element-binding proteins that are also bound by the T alpha 1 element of the human TCR alpha enhancer and the decamer element present in a large number of human and murine TCR beta promoters. Similarly, the T beta 5 TCR beta-enhancer element and the T alpha 2 TCR alpha-enhancer element bind at least one common T-cell nuclear protein. Taken together, these results suggest that TCR beta gene expression is regulated by the interaction of multiple T cell nuclear proteins with a transcriptional enhancer element located 3' of the C beta 2 gene and that some of these proteins may be involved in the coordinate regulation of TCR alpha and beta gene expression.
 ...
PMID:Identification and functional characterization of the human T-cell receptor beta gene transcriptional enhancer: common nuclear proteins interact with the transcriptional regulatory elements of the T-cell receptor alpha and beta genes. 214 10

Two spontaneous outgrowing Epstein-Barr virus (EBV)-carrying lymphoblastoid cell lines (LCLs), CG2 and CG3, have been established from bone marrow cells of myeloid leukemia patients. CG2 was derived from a patient with chronic myelomonocytic leukemia (CMMoL) and who has a 45 XO karyotype. CG3 was derived from a patient with juvenile chronic myeloid leukemia (CML) and who carries a hypotetraploid karyotype, 91XXYY. Both CG2 and CG3 cells carry the same type of translocation; t(1;19)(q23;p13). Both cell lines are of an early B cell lineage as shown by their reactivities with monoclonal antibodies OKIa, B1, B2 and B4. The combination of horizontal discontinuous agarose slab gel and Southern hybridization results show CG2 and CG3 cells are of monoclonal origin and harbor episomal EBV genomes. Approximately 50 EBV genome equivalents were contained in CG2 and CG3 cells. Immunofluorescence studies demonstrate the expression of EBV-encoded antigen (EBNA) in almost all cells of these two lines. The expression of EA and VCA is only observed in a small percentage of cells and cannot be induced by treatment with TPA and SB. Therefore, CG2 and CG3 cells are probably nonproducer cell lines for EBV. The serum samples from both patients have been shown to contain elevated IgG antibody titers to EBV antigens. Both cells are found to be nontumorigenic in nude mice. These cells may provide an important tool in analyzing molecular epidemiological aspects of EBV infections in diseases such as CMMoL and juvenile CML.
 ...
PMID:Characterization of two newly established EBV-containing lymphoblastoid cell lines from patients with myeloid leukemias. 215 89

A patient with chronic myeloid leukemia secreted an antibody to blood group glycosyltransferases after ABO-incompatible bone marrow transplantation (B recipient/O donor). Peripheral B lymphocytes from the recipient were transformed with Epstein-Barr virus, and then fused by polyethylene glycol with mouse myeloma cell line P3-X63/Ag8.653. After the cloning of the hybridoma cells, a cell line which produced human IgM antibody to blood group glycosyltransferases was established. The antibody completely neutralized B transferase activity at low concentration, while a larger amount of immunoglobulins was required to neutralize A transferase activity.
 ...
PMID:Monoclonal antibody to blood group glycosyltransferases, produced by hybrids constructed with Epstein-Barr-virus-transformed B lymphocytes from a patient with ABO-incompatible bone marrow transplant and mouse myeloma cells. 217 79

The possible presence of tumor cells in remission bone marrow (BM) is one of the major problems for the success of autologous BM transplantation (ABMT), because the reinfusion of viable malignant cells may result in relapse. In this study we attempted the purging of the malignant cells by the use of VP-16-213 (VP-16) and nitrogen mustard (NM) either alone or in combination. Four cell lines from various hematological malignancies were utilized: SK-DHL-2 was established from a B-cell diffuse histiocytic lymphoma; RAJI was from an Epstein-Barr virus (EBV)-infected B-cell lymphoma cell line; K-562 were from a chronic myelogenous leukemia (CML) blastic crisis; and HL-60, derived from a human promyelocytic leukemia, were used in exponential growth phase. Four logs of tumor cell-elimination were observed after 1-h incubation of RAJI cells with 25 micrograms/ml of VP-16. K-562 and SK-DHL-2 cells showed a greater than 4 logs reduction after 1-h exposure to 75 micrograms/ml of VP-16, and HL-60 cell line growth was inhibited by 3.2 logs. Under the same conditions (i.e., the treatment with 75 micrograms/ml), we observed a mean recovery of 2.7% of BM granulocyte-macrophage colonies (granulocyte-macrophage colony-forming units, CFU-GM), 3.2% of erythroid (erythroid burst-forming units, BFU-E), and 2.5% of pluripotent (granulocyte erythrocyte macrophage megakaryocyte colony-forming units, CFU-GEMM) progenitors, respectively. More than 3 logs reduction of leukemia and lymphoma cell lines were reached following 1-h treatment with 1 micrograms/ml of NM. After exposure to the same concentration of the drug we obtained 2.5% CFU-GM, 1.2% BFU-E, and 2% CFU-GEMM recovery. A drug mixture containing constant doses of VP-16 (10 and 20 micrograms/ml) and NM (1 micrograms/ml) reduced HL-60 and SK-DHL-2 cell growth to undetectable levels (i.e., 4 and 5 logs elimination) in the presence of an excess of irradiated BM cells, whereas it did not further affect the recovery of the BM precursors as compared to the single drugs used alone. These results suggest that the combination of these two drugs at the selected dose level could provide a better therapeutic index (i.e., higher tumor cell killing coupled with no additional cytotoxic effect on normal BM cells) than the same chemotherapeutic agent used alone and that this mixture may be useful for the "ex vivo" treatment of BM grafts.
 ...
PMID:In vitro cytotoxicity of VP-16-213 and nitrogen mustard: agonistic on tumor cells but not on normal human bone marrow progenitors. 239 48

We established a B lymphocyte line from bone marrow cultures of a patient with Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia. The cell line (MB) is positive for Ph1 and has the phenotype of mature B lymphocytes transformed by the Epstein-Barr virus (EBV). When DNA was isolated and hybridized to specific cDNA probes, a rearranged immunoglobulin gene and EBV-sequences were detected. On Western blots of cell extracts, the novel fusion protein (P 210) was demonstrated with antisera against bcr and v-abl proteins. These results confirm the concept that B lymphocytes in CML can be involved in the malignant clone and demonstrate that these B cells express the fusion protein.
 ...
PMID:A Ph1 chromosome positive B cell line expresses the fusion protein P 210. 249 56

An altered c-abl protein (P210) bearing increased tyrosine kinase activity represents the product of the hybrid bcr/c-abl gene arising as a consequence of the Philadelphia (Ph1) chromosome translocation, the consistent cytogenetic abnormality of chronic myelogenous leukemia (CML). Although the chronic phase of this disease is substantially characterized by a marked proliferation of myeloid cells, the Ph1 translocation occurs in an early multipotent stem cell, giving rise to both myeloid and lymphoid cell lineages. Here we show that P210 bcr/abl protein expression varies greatly in different Ph1 chromosome positive B-lymphoid cell lines obtained from Epstein-Barr virus-transformed lymphocytes of a CML patient in the chronic phase. In addition Ph1 positive and Ph1 negative lymphoid cell lines obtained from the same patient were tested for a number of biological properties including the immunophenotype, the capacity to grow in soft agar and possible tumorigenicity in nude mice. No differences were found.
 ...
PMID:Expression of the hybrid P210 bcr/abl protein in Philadelphia chromosome positive B-lymphoid cell lines. 251 Oct 93

Peripheral blood mononuclear cells from a patient with chronic myelogenous leukemia (CML), in remission, were depleted of CD8-positive T-cells and cultured with Epstein-Barr virus. Four of 20 cultures (20%) secreted human IgG antibodies selectively reactive with the cell surfaces of certain human leukemia cell lines. Three polyclonal, Epstein-Barr virus-transformed, B-cell lines were expanded and fused with the human-mouse myeloma analogue HMMA2.11TG/O. Antibody from secreting clones HL 1.2 (IgG1), HL 2.1 (IgG3), and HL 3.1 (IgG1) have been characterized. All three react with HL-60 (promyelocytic), RWLeu4 (CML promyelocytic), and U937 (monocytic), but not with KG-1 (myeloblastic) or K562 (CML erythroid). There is no reactivity with T-cell lines, Burkitt's cell lines, pre-B-leukemia cell lines, or an undifferentiated CML cell line, BV173. Leukemic cells from two of seven patients with acute myelogenous leukemia and one of five with acute lymphocytic leukemia react with all three antibodies. Normal lymphocytes, monocytes, polymorphonuclear cells, red blood cells, bone marrow cells, and platelets do not react. Samples from patients with other diverse hematopoietic malignancies showed no reactivity. Immunoprecipitations suggest that the reactive antigen(s) is a lactoperoxidase iodinatable series of cell surface proteins with molecular weights of 42,000-54,000 and a noniodinatable protein with a molecular weight of 82,000. Based on these data these human monoclonal antibodies appear to react with myelomonocytic leukemic cells and may detect a leukemia-specific antigen or a highly restricted differentiation antigen.
 ...
PMID:Human monoclonal antibodies reactive with human myelomonocytic leukemia cells. 292 15


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