lewis-x-antigen and Leukemia--Lymphoid

Expression of two developmentally regulated carbohydrate antigens, the sialyl stage-specific embryonic antigen-1 (SSEA-1) and I-antigens, in human lymphocytes and lymphocytic leukemia cells was investigated using specific monoclonal antibodies. Sialyl SSEA-1 was expressed only on natural killer (NK) cells, and was essentially absent on resting mature T and B cells among normal peripheral lymphocytes. On the other hand, the I-antigen was strongly expressed on virtually all mature B cells, moderately expressed on most mature T cells, but not expressed on NK cells in normal donors. Expression of the two antigens on normal T and B cells was reversible; in vitro stimulation of normal lymphocytes with concanavalin A (Con A) resulted in the loss of I-antigen and appearance of sialyl SSEA-1 on CD3+ T blasts, whereas stimulation with pokeweed mitogen led to loss of I-antigen expression and appearance of sialyl SSEA-1 antigen on CD19+ B blasts. Among lymphocytic leukemia cells, sialyl SSEA-1 was detected primarily on leukemia cells having immature properties such as most common acute lymphocytic leukemia (cALL) blasts, while the I-antigen was frequently expressed on malignant cells having relatively mature properties, such as those found in adult T-cell leukemia or chronic lymphocytic leukemia, and only occasionally on cALL blasts. Among normal peripheral lymphocytes, the sialyl SSEA-1+I-antigen- NK cells selectively underwent E-selectin (ELAM-1, endothelial-leukocyte adhesion molecule-1)-dependent adhesion to endothelial cells, while the I-antigen+sialyl SSEA-1- mature T and B cells did not, in line with the recent finding that sialyl SSEA-1 serves as a specific ligand for E-selectin. Con A blasts, which are sialyl SSEA-1+I-antigen-, also exhibited significant E-selectin-dependent adhesion to endothelial cells. These results indicate that expression of the sialyl SSEA-1 and I-antigens varies alternately depending on the differentiation/activation status of the lymphocytes, and that this at least partly regulates the behavior of lymphocytes at the vessel wall.

Topics: Antibodies, Monoclonal; B-Lymphocytes; Carbohydrate Sequence; Carbohydrates; Cell Adhesion; Cell Differentiation; Cell Line; Concanavalin A; Endothelium, Vascular; Glycosphingolipids; Humans; Killer Cells, Natural; Leukemia, Lymphoid; Lewis X Antigen; Lymphocyte Activation; Lymphocytes; Molecular Sequence Data; Pokeweed Mitogens; T-Lymphocytes

To increase our knowledge of the clonal relationship of leukaemia relapse, the genotypes and phenotypes of ten children with acute lymphoblastic leukaemia (ALL) were examined at initial diagnosis and relapse. Seven patients were phenotyped as common ALL, two as mixed, and one as T-cell ALL (T-ALL). Comparative analyses of immunoglobulin (Ig) heavy and light chain as well as T-cell receptor beta-chain (T beta) sequences revealed clonal variations, i.e. appearance of a novel or an evoluted leukaemic cell clone in five patients coinciding with the loss of common acute lymphoblastic leukaemic antigen (CALLA) in four cases, irrespective of early or late relapse. Conversion of early B- to T-ALL or lymphoblastic to non-lymphoblastic leukaemia was not noted in any of the patients examined. Our results suggest that clonal variation is a frequent event in childhood ALL.

Topics: Antigens, Differentiation; Antigens, Neoplasm; B-Lymphocytes; Child; Clone Cells; Genotype; Humans; Immunoglobulins; Leukemia, Lymphoid; Lewis X Antigen; Neprilysin; Phenotype; Receptors, Antigen, T-Cell; Recurrence; T-Lymphocytes

To determine the clinical importance of immunophenotypes in adult acute lymphoblastic leukemia (ALL), we prospectively studied 76 patients with this condition. Before treatment, lymphoblasts were tested for reactivity with monoclonal antibodies to B-cell, T-cell, and myeloid (My) antigens. Unexpectedly, myeloid antigens (MCS-2 or MY9) were identified in 25 patients (33 percent), usually in conjunction with B-cell or T-cell antigens. Among My+ patients, 15 (60 percent) expressed B-cell antigens (B+T-My+); all 6 tested had rearranged immunoglobulin genes. Five patients (20 percent) expressed T-cell antigens (B-T+My+), and one My+ patient expressed both B-cell and T-cell antigens. Only myeloid antigens (B-T-My+) were expressed in four patients (16 percent); three who were tested had germ-line immunoglobulin and T-cell-receptor gene configurations. Although no significant differences in presenting clinical features were found, My+ patients had fewer complete remissions than My- patients (35 vs. 76 percent, P less than 0.01). No differences in response or survival were observed between My+ and My- patients expressing T-cell antigens. However, among those expressing B-cell antigens, My+ patients had fewer complete remissions (29 vs. 71 percent, P = 0.02) and shorter survival (P = 0.03; median, 8.1 vs. greater than 26 months). These findings indicate that expression of myeloid antigen identifies a high-risk group of patients with adult ALL for whom alternative forms of treatment should be investigated.

Topics: Adult; Antigens, Neoplasm; Antigens, Surface; B-Lymphocytes; Humans; Leukemia, Lymphoid; Lewis X Antigen; Phenotype; Prognosis; Prospective Studies; Receptors, Antigen, T-Cell; Remission Induction; T-Lymphocytes

The carbohydrate antigen 3-fucosyl-N-acetyl-lactosamine (FAL) is expressed on human granulocytes and is detected by a monoclonal antibody B4.3. After neuraminidase treatment, this structure can also be detected on monocytes and on the cells of nearly all acute myeloid leukemia patients (38/39). It is then also present on the cells of a number of CALLA-positive lymphatic leukemias (8/18), but not on T-ALL and B-ALL cells. On cells of patients with AUL, the antigen is then detected in many TdT+ cases, but not in TdT- cases.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Cells, Cultured; Epitopes; Granulocytes; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lewis X Antigen; Neuraminidase; Oligosaccharides

The 3-fucosyl-N-acetyllactosamine structure, a sugar sequence contained in the human milk oligosaccharide lacto-N-fucopentaose III, is recognized by most of the granulocyte-specific monoclonal antibodies (MoAb) reported in the literature, including the six MoAb from our laboratory. Blast cells from patients with acute myeloblastic leukemia (AML) displayed a heterogeneous reaction pattern when they were exposed to MoAb against this moiety, and the proportion of reactive cells in individual cell samples was highly variable. The intensity of the reaction was strongly enhanced by neuraminidase treatment of AML blasts, and reactive structures were exposed on previously negative AML blast cells. Surprisingly, this granulocyte-associated antigen was exposed by desialylation not only on malignant myeloid precursor cells but also on common acute lymphoblastic leukemia cells. No such effect was seen when normal peripheral blood lymphocytes, lymphocytes from patients with chronic lymphatic leukemia, or blast cells from patients with B-cell acute lymphoblastic leukemia, acute erythroid leukemia, and acute megakaryoblastic leukemia were treated with neuraminidase.

Topics: Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Blood Platelets; Cell Line; Epitopes; Humans; Hybridomas; Immunoglobulin M; Leukemia, Lymphoid; Leukocytes; Lewis X Antigen; Mice; Mice, Inbred BALB C; Neuraminidase; Oligosaccharides; Plasmacytoma; Reference Values; Sialic Acids