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J Minowada

Publications and source records attributed to J Minowada.

At least 181 records · Page 10Linked to original sources
PubMed1984

Lineage infidelity of a human myelogenous leukemia cell line.

We have analyzed the organization and expression of the immunoglobulin heavy and light chain gene in the human myeloblastic leukemic sublines, ML1, ML2, and ML3, and in the human myeloid leukemic cell lines, HL-60, U937, THP1, and K562. ML1, ML2, and ML3 cells, despite a predominant granulocytic phenotype, express a rearrangement of the immunoglobulin heavy chain gene that typically occurs during the early stages of the B cell differentiation pathway. No rearrangement was found in any of the other cell lines tested. These findings strongly support the notion that, at least in some cases, acute myeloid leukemia (AML) cells represent highly atypical cells with profoundly altered gene expression, rather than cells arrested at a well-defined stage of the myeloid lineage.

Antibodies, Monoclonal↗
PubMed1984

Lack of T cell antigen expression on hairy cells of B cell origin after in vitro exposure to PHA.

The malignant monoclonal population in hairy cell leukemia (HCL) has been variously ascribed to be of myeloid, B, or even T cell origin. Recent data have been interpreted as suggesting that hairy cells (HC) may concomitantly or serially express both B and T surface determinants, a phenomenon which, if verified, would be unique among the lymphoproliferative malignancies. Data described here, however, demonstrate that (1) at least the majority of HCL are phenotypically of B cell derivation, and (2) the initial B cell phenotype is retained and solely expressed on cultured as well as phytohemagglutinin (PHA) activated monoclonal malignant HC.

Adult↗
PubMed1984

Enzyme markers in acute leukemias: advances during the last decade.

Besides the recent advances in immunology that provided important information for the characterization of leukemia cells, enzyme marker analysis is another area of progress in leukemia research. Assays of enzyme activities, both quantitative enzyme levels and qualitative isozyme changes, are of value in the classification of leukemias. The interest in the study of enzyme markers is due not only to technical improvements and new biochemical possibilities, but also to the involvement of enzyme marker analysis in the so-called "multiple marker analysis," which combines traditional and recently developed techniques in leukemia research. The aims of this review are to describe well-known and potential enzyme markers as well as to stress the relevance of enzyme marker analysis combined with multiple marker analysis for leukemia subclassification and the understanding of normal hematopoietic cell differentiation.

5'-Nucleotidase↗
PubMed1984

Modulation of cell surface antigens induced by 12-O-tetradecanoyl-phorbol 13-acetate in two myeloblastic cell lines, a promyelocytic cell line, and a monoblastic cell line: detection with five monoclonal antibodies.

The modulation of cell surface antigens in 2 myeloblastic cell lines (ML-1 and KG-1), a promyelocytic cell line (HL-60), and a monoblastic cell line (THP-1-0) by the presence of 12-O-tetradecanoyl-phorbol 13-acetate [(TPA) CAS: 16561-29-8] was investigated by indirect membrane immunofluorescence with the use of three monoclonal antibodies (MoAb) (OKM-1, 63D3, and MCS-2) reacting with myeloid-monocyte antigens (expressed by cells of both granulocyte and monocyte lineages) and two MoAb (1/12/13 and MCS-1) reacting with myeloid antigens (expressed by cells of the granulocyte lineage). Functionally mature macrophage properties, such as adherence, morphologic character, and phagocytosis, were induced by the presence of TPA in each of the cell lines except for adherence in the HL-60 cells. After 3 days in culture, the expression of the OKM-1-defined antigen was markedly augmented in all 4 cell lines. The expression of the 63D3-defined antigen was also markedly augmented in the ML-1, KG-1, and THP-1-0 cells, but it was not significantly altered in the HL-60 cells. The MCS-2-defined antigen was amplified in expression in the ML-1 and HL-60 cells, but it showed minimum decrease in the KG-1 and THP-1-0 cells. The MCS-1-defined antigen expression was suppressed in ML-1, HL-60, and THP-1-0 but was enhanced in KG-1. The suppressed expression of My-1 antigen (detected by the MoAb 1/12/13) was noted in all 4 cell lines. Thus in the ML-1 cells, expression of the myeloid-monocyte antigens was augmented, whereas myeloid antigen expression was inhibited in the presence of TPA, a result that parallels antigenic expression in terminal macrophage differentiation. The trend was true, except for the 4 cell line-antigen combinations (MCS-2-defined antigen and MCS-1-defined antigen in KG-1, 63D3-defined antigen in HL-60, and MCS-2-defined antigen in THP-1-0). The heterogeneous attitude of some antigens to TPA found in these cell lines may result from the fact that they represent different points in the myeloid-monocyte differentiation scheme.

Antibodies, Monoclonal↗
PubMed1984

Distinctive sensitivity of some T-leukemia cell lines to L-asparaginase.

Forty-two human hematopoietic cell lines were assessed for sensitivity to a four-day incubation with L-asparaginase. Eight of 13 T-leukemia cell lines and 1 of 7 non-T, non-B common acute lymphoblastic leukemia cell lines exhibited an ID50 (50% growth inhibition dose) of less than 0.0001 IU/ml. Seven of these sensitive cell lines were further cultured in L-asparagine-free medium and were found not to proliferate. Five T-leukemia cell lines, 6 non-T, non-B common acute lymphoblastic leukemia cell lines, 10 "abnormal" B-cell lines, 4 "normal" B-cell lines, 3 myeloma cell lines and 5 myeloid leukemia cell lines had ID50 values between 0.1 and 1.0 IU/ml. Twelve of these resistant cell lines were able to proliferate in L-asparagine-depleted medium. The results indicate that some patients with T-cell acute lymphoblastic leukemia might respond to this enzymatic antineoplastic drug, L-asparaginase, at low dose.

Asparaginase↗
PubMed1984

Benign monoclonal B cell lymphocytosis--a benign variant of CLL: clinical, immunologic, phenotypic, and cytogenetic studies in 20 patients.

From 1951 through 1978, we have seen 20 cases of stage O chronic lymphocytic leukemia (CLL) without disease progression for 6.5-24 years. The cohort included 7 males and 13 females, aged 48-77 years at the time of diagnosis. None presented with anemia, thrombocytopenia, or neutropenia nor developed cytopenias during follow-up. Mean total lymphocyte count in these patients was 20,100/microL, with ranges from 10,000 to 43,700 at the time of diagnosis, and was 20,600, with ranges from 1,000 to 47,200, at last follow-up. Of 12 patients studied, 8 and 4 were phenotyped as heavy chain mu delta- and mu-type, respectively, with 7 kappa- and 4 gamma-type (no light chain was detectable in one patient). Of 13 patients studied, one had a slightly elevated IgG level and two had slightly depressed serum IgA and IgM levels. All patients had positive delayed hypersensitivity responses to at least one of five skin test antigens. Each of seven patients studied for an in vitro leukocyte thymidine uptake had a low level of [3H]thymidine incorporation. Nine of 12 patients studied had elevated total T cells, and the remaining 3 had normal T cell counts. In vitro unseparated lymphocyte response to phytohemagglutinin showed normal kinetics of DNA synthesis, with a peak response on day 3 or 4 of culture in 4 and slightly or moderately depressed and/or delayed kinetics in 8 patients studied. Cytogenetic analyses by Q- or G-banding techniques of polyclonal B cell mitogen-stimulated lymphocytes in all six patients studied showed normal karyotypes. These data are consistent with a previously undescribed syndrome involving a monoclonal B cell lymphocytosis, a prolonged asymptomatic or benign clinical course, and essentially normal humoral and cellular immunity and normal karyotype. Our observations indicate that these 20 patients with stage O CLL have a benign clinical course and that they may also be designated as benign monoclonal B cell lymphocytosis ( BMBL ), a benign variant of CLL.

Aged↗
PubMed1984

Determination of cell surface membrane antigens common to both human neuroblastoma and leukemia-lymphoma cell lines by a panel of 38 monoclonal antibodies.

The surface membrane antigens of 7 neuroblastoma and 91 leukemia-lymphoma cell lines were studied with the use of a total of 36 murine monoclonal antibodies (MoAb) primarily developed against hematopoietic cells and 2 MoAb developed against human fetal brain. Five of the MoAb against hematopoietic cells (BA-1, BA-2, DU-ALL-1, J-5, and BA-3) consistently bound to common acute lymphoblastic leukemia cell lines, and 2 others (MCS-2 and OKM-1) reacted uniformly with acute myeloblastic-acute monoblastic leukemia cell lines. However, these 7 MoAb also reacted with 1-7 neuroblastoma cell lines. All the human neuroblastoma cell lines bound MoAb BA-2 and DU-ALL-1. Six of the 7 lines reacted with BA-1. Only 1 neuroblastoma cell line (SJ-N-CG) gave positive staining with J-5 and BA-3, and another line (SK-N-AS) bound MoAb MCS-2 and OKM-1. Anti-fetal brain MoAb (UJ-13A and UJ-127-11) were highly positive for all the neuroblastoma cell lines. By contrast, 4 of 43 leukemia-lymphoma cell lines tested bound these anti-fetal brain antibodies. Both B3/25 and OKT-9, anti-transferrin receptor antibodies, reacted with all of the hematopoietic and neuroblastoma cell lines. These results demonstrate that neuroblastoma and hematopoietic cell lines possess common antigenic determinants despite their different embryologic origins. The neuroblastoma cell lines may be classified into subgroups on the basis of phenotype profiles determined by the MoAb. MoAb may be useful in characterization and classification of neuroblastoma cells, as has already proved to be the case for cells of the hematopoietic lineages.

Antibodies, Monoclonal↗
PubMed1983

Lymphoid blast crises of chronic myelogenous leukemia represent stages in the development of B-cell precursors.

The origin and stage of differentiation of the blast-crisis cells in chronic myelogenous leukemia have remained uncertain. Because immunoglobulin heavy-chain and light-chain genes must undergo a DNA rearrangement during B-cell development but rarely do so in human non-B-cell lineages, we examined these genes in 18 episodes of chronic myelogenous leukemia. In eight of nine episodes of lymphoid blast crisis, heavy-chain genes were rearranged, and in three, rearrangements in light-chain genes were also present. In contrast, cells from chronic myeloid, myeloid blast, and erythroid-like phases retained germ-like immunoglobulin genes. The observed phenotypic markers and gene configurations revealed that most lymphoid blast crises represent stages of development of B-cell precursors. In two separate episodes of lymphoid crisis, cells from a single patient possessed identical heavy-chain but different light-chain-gene configurations. Thus, the precursor cells that monoclonally expand to produce a lymphoid crisis are capable of immunoglobulin-gene rearrangements and represent discrete steps in early B-cell maturation.

Antigens, Surface↗
PubMed1983

Differential ability of mitogen-stimulated human leukocyte-conditioned media to induce Fc receptors in human leukemia cells.

The ability of mitogen-stimulated human leukocyte-conditioned media (M-CM) to induce the in vitro differentiation of various human leukemic cell lines was evaluated by measuring the appearance of Fc receptors (FcR) through their ability to form EA rosettes. Only cells of myeloid lineage were induced by M-CM to express FcR; T-, and B-, and non-T/non-B cells failed to respond. As determined with ML-1, a line of human myeloblastic leukemia cells, pokeweed mitogen-conditioned medium, at concentrations of 1-10%, stimulated the expression of FcR in 70-98% of the cells within 1 day after treatment. Phytohemagglutinin-, concanavalin A-, and lipopolysaccharide-conditioned media were less active. The FcR-inducing activity was partially separated from M-CM by chromatography on Sephadex G-75. It was stable between pH 4 and 10, and lost activity at temperatures above 40 degrees C.

Cell Line↗
PubMed1983

Some T-cell leukemia lines express surface markers related to a restricted set of human VH determinants.

Serological studies were carried out to obtain information regarding the relationship of the VH-related determinants expressed by certain permanent in vitro T-cell leukemia lines and corresponding determinants expressed by characterized human serum immunoglobulins. A panel of conventional (goat and rabbit) antisera, produced against various Fab-related fragments of monoclonal human Waldenstrom macroglobulins and polyclonal IgG molecules, bound to certain in vitro T-cell leukemia lines, notably, 70-N2, MT-1, YT4E, and HUT78, as shown by microhemagglutination. Inhibition studies using characterized myeloma proteins to inhibit this agglutination indicated the expression of a restricted VH-related determinant by these T-cell lines. Parallel studies performed using conventional (rabbit) and murine monoclonal/hybridoma antibodies produced against the isolated 68,000-Da VH-related product synthesized by the 70-N2 line showed that the determinant expressed by this molecule was restricted in expression, comprising 2-3% of the normal, polyclonal human Fab pool, and that the determinants found on the other positive T-cell leukemias were cross-reactive rather than identical. The inhibition studies suggest that the determinant resides between residue 22 and the end of the VH region. These results further define the antigenic nature of the VH-related marker found on the surfaces of certain normal and neoplastic T-cell lines.

Animals↗
PubMed1983

Isolation and transmission of human retrovirus (human t-cell leukemia virus).

Nine new isolates of human T-cell leukemia-lymphoma virus (HTLV) were obtained from cells of seven patients with malignancies of mature T cells and from two clinically normal relatives of a T-cell leukemia patient. These people were from the United States, Israel, the West Indies, and Japan. The virus was detected in the fresh T cells and was isolated from the established T-cell lines. Each isolate is closely related to the first HTLV isolate, and all the new HTLV isolates were transmitted into normal human T cells obtained from the umbilical cord blood of newborns.

Cell Line↗
PubMed1983

Differential selectivity of 5-fluorouracil and 5'-deoxy-5-fluorouridine in cultured human B lymphocytes and mouse L1210 leukemia.

The role of differential metabolic activation of a 5-fluorouracil (FU) prodrug, 5'-deoxy-5-fluorouridine (dFUR), in achieving selective cytotoxicity was investigated in cultured human (dFUR), in achieving selective cytotoxocity was investigated in cultured human B lymphocytes and murine leukemia L1210 cells. B cells were cross-sensitive to FU and dFUR. On the other hand, leukemia L1210 cells were sensitive to FU but resistant to dFUR. The difference in the biological activities of FU and dFUR in B and L1210 cells correlated with (a) the metabolism of dFUR to FU by intact B (60% conversion) and L1210 (no conversion) cells, and (b) the phosphorylase activity of B (660 nmoles converted in 2 hr per mg protein) and L1210 (undetectable) cells. The intracellular metabolism of FU and dFUR was studied using a reversed-phase ion-pair high pressure liquid chromatographic assay. FU and dFUR shared similar metabolic pathways in B cells; their anabolites included FU ribose and deoxyribose nucleosides and nucleotides. In L1210 cells, FU was anabolized to 5-fluorouridine triphosphate and 5-fluorodeoxyuridine monophosphate, whereas dFUR was present mainly as the unchanged drug. Further metabolism studies using dFUR with tritium label in either the FU moiety or the altered sugar moiety established that the metabolic pathway of dFUR to cytotoxic FU anabolites in the B cells was via phosphorolysis to FU. These data indicate that, on a cellular level, an FU prodrug such as dFUR, which is activated by cytosolic enzyme, has a different selectivity from that of FU, and that the basis of differential selectivity is the initial phosphorolysis to FU.

Animals↗
PubMed1983

Surface morphology and membrane phenotype of cultured human leukemia-lymphoma cells. A scanning electron microscopic study of 36 cell lines.

Scanning electron microscopy and immunologic methods, to detect the expression of a variety of surface markers, were performed on cells from 36 established human leukemia-lymphoid cell lines. Attempts were made to correlate the surface morphologic findings with the membrane phenotype as determined by the presence or absence of a number of specific antigens and B- or T-cell markers. Thirteen of the cell lines were of the T-lymphoid type, 15 B-derived, and eight were defined as non-B non-T in nature. All the lines derived from patients with acute lymphoblastic leukemia (ALL) had similar surface topographies and generally displayed relatively smooth surfaces with few microvilli, while in some a proportion of moderately villous cells was evident. Burkitt's lymphoma cells tended to show more villous surfaces but, similar to circulating B-ALL cells, variable numbers of microvilli were frequently seen making consistent distinctions between this and other lymphoid leukemias difficult in individual cases. Two of the non-B non-T lines are known to be of erythroid (K-562) and myeloid origin (HL-60), respectively. In both these lines, cells with relatively few microprojections dominated; however, some showed transverse ridge-like profiles, a feature frequently encountered on circulating leukemic cells of myeloid type.

B-Lymphocytes↗
PubMed1983

The distribution of DR5, MT2, and MB3 specificities on human Ia subsets.

Human Ia molecules were isolated from cells of LG-38, an HLA-homozygous lymphoid cell line of DR5 specificity. Three Ia subsets could be distinguished and separated by using specific alloantisera and a monoclonal antibody with polymorphic reactivity. These subsets carried the specificities DR5 and MT2, MT2 alone and MB3 alone. The structure of the three molecular species was analyzed by microfingerprinting. The subset carrying only MT2 was similar, in both the component alpha and beta chains, to the major subset carrying DR5 and MT2, whereas the subset carrying MB3 was distinct in both chains from the other two subsets. These data are compatible with our previous findings obtained for the products of two Ia loci closely linked to the DR locus and provisionally called DC and BR; they also support the conclusion that the subset carrying only MT2 is an allelic product of the BR locus, whereas the MB3 subset is an allelic product of the DC locus. MT2 appears to be a shared specificity of DR and BR loci products.

Antibodies, Monoclonal↗
PubMed1983

A human B-cell line (BES-1) forming rosettes with sheep erythrocytes, producing Forssman antibody, and phagocytizing sheep erythrocytes.

A lymphoid cell line, designated BES-1, belonging to "lymphoblastoid cell lines with B-cell properties (B-LCL)" and derived from some normal B lymphocytes, was established in an attempt at primary culture of peripheral blood from a patient with acute myelogenous leukemia (AML). BES-1 cells unexpectedly formed rosettes with sheep erythrocytes (SRBC), which are usually a T-cell marker, and phagocytized SRBC. Subsequent study indicated that BES-1 cells produce antibody specific to Forssman (F) antigen, but not to Paul-Bunnell (P-B) or Hanganutzin-Deicher (H-D) antigen.

Adult↗