Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An increasing number of acute leukemias coexpressed markers normally believed to be restricted to a single lineage have been found recently. This special subgroup of leukemias have drawn a lot of attention because of their biologic and clinical significance. In a study of 100 consecutive de novo ANLL patients diagnosed by FAB criteria, T-cell antigen CD7 was identified on the leukemic blasts of 13 patients, ten of whom had M1 subtype of leukemia, myeloblastic leukemia without maturation. All the patients showed positive staining with myeloperoxidase and expressed myeloid markers CD13 and/or CD33, but lacked CD11b, a marker of more mature myeloid cells. Combined staining with myeloperoxidase and CD7 of the cells from four patients revealed coexpression of both markers on the same cells. None of the patients expressed the two other T-cell antigens CD2 or CD5. All ten patients who had DNA analysis showed germline configuration of TCR beta and gamma chain genes. One patient had chromosomal translocation involving 11q23, t(11; 19) (q23; p13), which is the site frequently associated with both myeloid and lymphoid malignancies. The clinical implications of this subgroup of patients need further study on more patients, and need longer follow-up.
 ...
PMID:A subset of acute nonlymphocytic leukemia with expression of surface antigen CD7--morphologic, cytochemical, immunocytochemical and T cell receptor gene analysis on 13 patients. 169 99

The human CD7 molecule is a 40-kDa member of the immunoglobulin gene superfamily that is expressed on T-lymphoid and myeloid precursors in fetal liver and bone marrow. CD7 is also expressed on T lymphocytes in multiple stages of T-cell development, including a major subset of mature peripheral T cells. In this paper we report the isolation and characterization of the human CD7 gene and 5' flanking region. Sequence analysis revealed that the CD7 gene comprises four exons that span 3.5 kilobases. The 5' flanking region (506 base pairs) has a high G + C content and no "TATA" or "CCAAT" elements. DNase I sensitivity analysis of chromatin from the CD7+ progenitor cell leukemia line, DU528, and the CD7-, CD4+, CD8+, TCR alpha beta + T-cell line, DU980 (where TCR is the T-cell receptor), revealed two distinct hypersensitive sites 5' of the CD7 gene. Hypersensitive site 1, present in the DU980 T-cell line, was located 4.5 kilobases upstream of the presumed CD7 transcription initiation site. Only DNase I hypersensitive site 2, which mapped to the promoter region, was found in the DU528 line. Comparison of the organization of the CD7 gene with that of other members of the immunoglobulin gene superfamily revealed that the human CD7 gene most closely resembles the murine Thy-1 gene. Both CD7 and Thy-1 are encoded by small genes with four exons, contain TATA-less promoters, and have a similar functional organization. These structural similarities suggest that human CD7 and murine Thy-1 may be functional homologues.
 ...
PMID:Isolation and characterization of the genomic human CD7 gene: structural similarity with the murine Thy-1 gene. 170 3

We have investigated the efficacy of a F(ab'gamma)2 bispecific antibody (BsAb) with dual specificity for the CD7 molecule in one Fab arm and for the ribosome inactivating protein (rip) saporin in the other arm, for delivering saporin to the acute T-cell leukaemia cell line HSB-2. Saporin titration experiments revealed that BsAb increased the toxicity of saporin 435-fold for HSB-2 cells, reducing the IC50 for saporin alone from 0.1 mumol to 0.23 nmol when BsAb was included. The rate of protein synthesis inactivation brought about by BsAb-mediated toxin delivery to HSB-2 cells was very similar to that described for conventional immunotoxins (IT's) with a t10 (time taken for a one log inhibition of protein synthesis compared with controls) of 46 h obtained at a saporin concentration of 1 nmol and 226 h at 0.1 nmol. BsAb titration studies demonstrated a clear dose response effect of BsAb concentration on target cell protein synthesis inhibition and cell proliferation. The absolute specificity of toxin delivery was unequivocally demonstrated by a failure of BsAb to deliver an effective dose of saporin to the CD7- cell line HL60 and by the blocking of BsAb-mediated delivery of saporin to HSB-2 cells with an excess of F(ab)2 fragments of the anti-CD7 antibody, HB2. These studies have clearly demonstrated the effectiveness of this BsAb for delivering saporin to a T-ALL cell line utilising CD7 as the target molecule on the cell surface. BsAb's would therefore appear to offer a realistic alternative to IT's for toxin delivery to tumour cells and may even offer certain advantages over conventional IT's for clinical use.
 ...
PMID:Characteristics and performance of a bispecific F (ab'gamma)2 antibody for delivering saporin to a CD7+ human acute T-cell leukaemia cell line. 171 53

Fourteen patients with high-risk T-lineage acute lymphoblastic leukemia (ALL) in complete remission underwent autologous bone marrow transplantation (BMT) in an attempt to eradicate their residual disease burden. A combined immunochemotherapy protocol using a cocktail of two immunotoxins directed against CD5/Tp67 and CD7/Tp41 T-lineage differentiation antigens in combination with the in vitro active cyclophosphamide congener 4-hydroperoxy-cyclophosphamide (4-HC) was used to purge autografts. Despite high dose pretransplant radiochemotherapy and effective purging of autografts, 9 of 14 patients relapsed at a median of 2.5 months (range, 1.2 to 16.8 months) post BMT. Two patients remain alive and disease free at 26 and 28 months post BMT. We used a novel quantitative minimal residual disease (MRD) detection assay, which combines fluorescence activated multiparameter flow cytometry and cell sorting with leukemic progenitor cell (LPC) assays, to analyze remission bone marrow (BM) samples from T-lineage ALL patients for the presence of residual LPCs. Notably, high numbers of residual LPC detected in remission BM before BMT constituted a poor prognostic indicator, providing the first evidence for the biologic significance and clinical value of in vitro T-lineage ALL LPC assays. The median value for the residual leukemia burden before BMT, was approximately 8.6 x 10(3) LPC/10(8) mononuclear cells (MNC) (approximately 0.0086% LPC). Patients with a residual leukemia burden less than this median value appeared to have a better outlook for remaining free of relapse after autologous BMT than patients with a greater leukemia burden (53 +/- 25% v 14 +/- 13%, P = .006, Mantel-Cox). By comparison, the log kill efficacy of purging, the remaining numbers of LPC in purged autografts, or the estimated numbers of reinfused LPC, did not correlate with the probability of disease-free survival (DFS). These results indicate that the primary reason for the recurrence of leukemia was inefficient pretransplant radiochemotherapy rather than inefficient purging of autografts.
 ...
PMID:Autologous bone marrow transplantation in high-risk remission T-lineage acute lymphoblastic leukemia using immunotoxins plus 4-hydroperoxycyclophosphamide for marrow purging. 222 22

The principal characteristics of monoclonal antibodies (MCA) ICO have been presented. The MCA ICO panel includes MCA against differentiating antigens of T- and B-lymphocytes, myelomonocytes, human leukemia-associated antigens. The following MCA have been described: MCA ICO-87 against common T-cell antigen CD7, ICO-33 and ICO-80 against common T-cell antigen CD5, MCA ICO-10 against Thy-1 antigen of early thymocytes, ICO-44 against CD1c antigen of cortical thymocytes, MCA ICO-90 against CD3 antigen of mature T-lymphocytes, MCA ICO-86 against CD4 antigen of T-helper/inductor cells, MCA ICO-31 against CD8 antigen of T-suppressor/cytotoxic cells, MCA ICO-1 against nonpolymorphic antigens of HLA II class, MCA ICO-12 against CD22 antigen of B-lymphocytes, MCA ICO-30 against mu-chain of human IgGM, MCA ICO-66 against CD37 antigen of B-lymphocytes, MCA ICO-88 against antigen of activated T- and B-cells, MCA ICO-35 against lymphoblasts, MCA ICO-88 against CD38 antigen of thymocytes and activated cells.
 ...
PMID:[Monoclonal antibodies of the ICO series against differentiation antigens of human lymphocytes]. 225 63

A human leukemia T-cell line (PF-382) spontaneously derived from the pleural effusion of a child with T-cell acute lymphoblastic leukemia is described. The cell line, which has been maintained in culture for over 10 months, has a modal number of 46 chromosomes and is characterized by a chromosomal abnormality, present in most of the cells, consisting of a translocation between chromosome X and chromosome 15 (46X,Xq-,15p+). The cells are not recognized by the OKT3 and OKT11 monoclonal antibodies (MoAb), nor do they form rosettes with sheep erythrocytes. By contrast, they react with the OKT6, Leu-1, and Leu-9 MoAb, which detect early T-lymphocytes, and express the more mature OKT8 antigen. The presence of the OKT8 marker is associated with suppressor activity on the pokeweed mitogen-induced proliferation and differentiation of normal B-cells, both by the PF-382 cells and by their supernatant. However, no cytotoxic activity against natural killer (NK)-sensitive target cells (K562) was found, indicating that the proliferating cells do not correspond to the subset of NK cells expressing the OKT8 antigen. Furthermore, the cells are incapable of both spontaneous and mitogen-induced interleukin-2 and interferon production. The ability of the PF-382 cell line to release a soluble factor(s) capable of modulating the differentiation of the B-cell compartment suggests that this new cell line represents a valuable model for the investigation of the interrelationships between T-cell subsets and other hematopoietic cell lineages.
 ...
PMID:A novel leukemia T-cell line (PF-382) with phenotypic and functional features of suppressor lymphocytes. 241 Jun 52

Monoclonal antibody Leu-9 (CD 7) has been reported to be a sensitive and specific marker for T-cell lineage in leukemic processes, since it is positive in patients whose leukemic cells fail to express other T-cell antigens. To test whether Leu-9 is indeed specific for T-cell leukemias, we examined in detail 10 cases of acute leukemia in which reactions were positive for Leu-9 and negative for other T-cell-associated markers including T-11, Leu-1, T-3, and E-rosettes. Morphologically and cytochemically, 2 of these 10 leukemias were classified as lymphoblastic, 4 as myeloblastic, 2 as monoblastic, 1 as megakaryoblastic, and 1 as undifferentiated. The case of acute megakaryoblastic leukemia is the first reported case to be Leu-9 positive. None of the 10 were TdT positive. Of six cases (two monoblastic, one lymphoblastic, one myeloblastic, one megakaryoblastic, and one undifferentiated) in which we evaluated for DNA gene rearrangements, only one, a peroxidase-positive leukemia, showed a novel band on study of the T-cell-receptor beta-chain gene. We therefore conclude that Leu-9 is not a specific marker to T-cell lineage and that, in the absence of other supporting data, Leu-9 positivity should not be used as the sole basis of classifying an acute leukemia as being T-cell derived.
 ...
PMID:Leu-9 (CD 7) positivity in acute leukemias: a marker of T-cell lineage? 247 73

Important insights into leukocyte differentiation and the cellular origins of leukemia and lymphoma have been gained through the use of monoclonal antibodies that define cell surface antigens and molecular probes that identify immunoglobulin and T cell receptor genes. Results of these studies have been combined with markers such as surface membrane and cytoplasmic immunoglobulin on B lymphocytes, sheep erythrocyte receptors on T lymphocytes, and cytochemical stains. Using all of the above markers, it is now clear that acute lymphoblastic leukemia (ALL) is heterogeneous. Furthermore, monoclonal antibodies that identify B cells, such as the anti-B1 and anti-B4 antibodies in combination with studies of immunoglobulin gene rearrangement, have demonstrated that virtually all cases of non-T-ALL are malignancies of B cell origin. At least six distinct subgroups of non-T-ALL can now be identified. T-ALL is subdivided by the anti-Leu-9, anti-Leu-1, and antibodies that separate T lymphocyte subsets into three primary subgroups. Monoclonal antibodies are also useful in the subclassification of non-Hodgkin's lymphoma, and certain distinct markers can be correlated with morphologic classification. The cellular origin of the malignant Reed-Sternberg cell in Hodgkin's disease remains uncertain. A substantial number of investigators favor a myelocyte/macrophage origin based on cytochemical staining; however, consistent reactivity with antimonocyte reagents has not been demonstrated. Although monoclonal antibodies are useful in distinguishing acute myeloid from acute lymphoid leukemias, they have less certain utility in the subclassification of acute myelogenous leukemia (AML). Attempts to subclassify AML by differentiation-associated antigens rather than by the French-American-British (FAB) classification are underway in order to document the potential prognostic utility of surface markers. Therapeutic trials using monoclonal antibodies in leukemia and lymphoma have been reported. Intravenous (IV) infusion of unlabeled antibodies is the most widely used method; transient responses have been demonstrated. Antibodies conjugated to radionuclides have been quite successful in localizing tumors of less than 1 cm in some studies. Therapy trials with antibodies conjugated to isotopes, toxins, and drugs are currently planned. Purging of autologous bone marrow with monoclonal antibodies and complement in vitro has been used in ALL and non-Hodgkin's lymphoma; preliminary data suggest that this approach may be an effective therapy and may circumvent many of the obstacles and toxicities associated with in vivo monoclonal antibody infusion.
 ...
PMID:Immunologic classification of leukemia and lymphoma. 294 Oct 82

The ML cell lines (ML-1, -2, and -3) were derived from the cells of a patient with T-cell malignant lymphoma who developed acute myeloblastic leukemia and whose cells showed a primary chromosome change at band 11q24. Surface marker studies of the ML cells showed that they had both myeloid (MCS-1, MCS-2, and OKM-1) and some T-lymphocyte (3A1/Leu-9 and OKT-4/Leu-3a) characteristics. Molecular studies on these lines were performed in order to determine the possible involvement of the Hu-ets-1 gene, since it is located at band 11q23----q24. All ML cell lines showed half the intensity of the Hu-ets-1 DNA bands as compared to those of controls (karyotypically normal B-cell lines). In contrast, DNAs from leukemia cells with t(4;11)(q21;q23) or t(1;11)(q21;q23 or q24) showed no rearrangement, deletion, or amplification of the ets-1 gene. These findings indicate that a chromosome region (11q24----qter), including the Hu-ets-1 gene, of the ML cells is deleted as a result of the primary cytogenetic change and that heterogeneity is present in the mechanism of human leukemia involving the 11q23----q24 region.
 ...
PMID:Loss of a Hu-ets-1 allele in human leukemia cell lines ML-1, -2, and -3 with a chromosome change at 11q24. 310 34

In this study, a monoclonal antibody (mAb) termed SN6 was generated by immunizing a mouse with a non-T-cell leukemia antigen preparation isolated from cell membranes of leukemia cells derived from a patient (FJ) with non-T/non-B-cell-type acute lymphoblastic leukemia (ALL). SN6 was tested against a variety of cultured and uncultured human cell specimens by using a sensitive cellular radioimmunoassay. Among the 26 cultured malignant and nonmalignant cell lines tested, SN6 reacted with all of the 6 leukemic non-T/non-B (including pre-B)-cell lines tested--i.e., KM-3, NALM-16, REH, NALL-1, NALM-1, and NALM-6. Of these cell lines, 5 were derived from individual patients with ALL; the remaining 1 was from a patient with chronic myelocytic leukemia in blast crisis. In addition, SN6 reacted with 3 of 3 leukemic myelo-monocytic cell lines tested--i.e., ML-2, HL-60, and U937. SN6 did not react with any other cell lines. A consistent result was obtained with 42 fresh (uncultured) cell specimens derived from individual patients with several different types of leukemias. SN6 reacted with 11 of 16 non-T/non-B (including pre-B)-cell ALL specimens. In addition, it reacted with various myelo-monocytic leukemia cell specimens to various degrees. SN6 did not show a significant reaction with normal peripheral blood cells tested, which included B cells, T cells, granulocytes, monocytes, and erythrocytes. However, it reacted with a small population (approximately 1% as determined by immunofluorescence staining) of normal bone marrow cells. The approximate molecular mass of the glycoprotein antigen defined by SN6 was determined to be 160,000 by radioimmunoprecipitation followed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Only one component of 80,000 daltons was formed upon reduction of the 160,000 molecular mass antigen. Therefore, this antigen is apparently a homodimer of a 80,000-dalton subunit. This conclusion was further corroborated by two-dimensional gel analysis, which showed a single well-defined spot for the reduced antigen. We designate this distinct human leukemia-associated cell surface antigen "GP160."
 ...
PMID:Distinct human leukemia-associated cell surface glycoprotein GP160 defined by monoclonal antibody SN6. 346 4


1 2 Next >>