Biomedical subjects

A Al-Katib

Publications and source records attributed to A Al-Katib.

31 records · Page 2Linked to original sources

PubMed1986

Surface immunoglobulin light chain expression in pre-B cell leukemias.

Cytofluorographic analysis of surface immunoglobulin (sIg) light chain clonal excess (CE), defined as (%kappa+ - %lambda+)/(%kappa+ + %lambda+) cells per discrete level of fluorescence intensity, was carried out on mononuclear cells of 32 leukemic patients. Eight demonstrated sIg light chain CE, including four blastic chronic myeloid leukemias (BL-CML), three "null" acute lymphoblastic leukemias (ALL), and one leukemic lymphoblastic lymphoma. Six of the leukemias demonstrated a kappa CE and two had a lambda CE. Sorted kappa+ PB cells from a BL-CML patient were shown to have a diploid DNA stem line and to bear the "common" ALL antigen. To provide further support for our finding of the expression of sIg light chains in ALL, we studied the REH cell line, derived from a "common" ALL patient and found cytoplasmic mu heavy chain and surface Ig lambda CE. Nucleic acid blotting experiments on REH revealed that both kappa genes had been deleted and that lambda genes had been rearranged, as expected in B cells expressing lambda light chains. Moreover, REH cells contained mu and lambda RNA. When REH cells were treated with TPA the amount of mu chain RNA increased by approximately fivefold and the amount of lambda chain RNA increased by approximately twofold. The finding of sIg light chain in pre-B cell leukemias and in the REH cell line, suggests that these leukemic cells are further differentiated along the B-cell lineage than was previously believed.

Antigens, Neoplasm↗

PubMed1986

Phase I trial of recombinant interferon gamma in cancer patients.

Interferon gamma (IFN-gamma) is a lymphokine with potent in vitro effects on cell growth and immune function. We have investigated the effects of rIFN-gamma (sp act approximately 2 X 10(7) U/mg, purity greater than 99%) in 16 evaluable patients with advanced malignancy in a phase 1 trial. Patients were treated with six-hour intravenous (IV) infusions daily, five days a week for 2 weeks. After a 2-week rest period, the IV treatment cycle was repeated. Responders were maintained on repeated IV treatment cycles or daily intramuscular (IM) injections. Patients were entered at fixed dose levels of 0.1, 0.5, or 1.0 mg/m2/d. The maximum safely tolerated dose was 0.5 mg/m2. The most common side effects were constitutional symptoms, including fever, chills, fatigue, and myalgias. Reversible and transient increases in hepatic transaminase and decrease in granulocyte counts were seen. Treatment was associated with a dose-dependent increase in serum levels of beta 2 microglobulin. Partial responses (PRs) were observed in one patient with Hodgkin's disease and one patient with chronic lymphocytic leukemia. Fairly constant levels of serum IFN were found at four and six hours during infusion, followed by a rapid decline within one to two hours. We conclude that rIFN-gamma can be safely administered by a six-hour IV infusion and that it can induce in vivo some of the biologic effects reported in in vitro studies.

Adult↗

PubMed1986

Cellular distribution of a B-cell specific surface antigen (gp54) detected by a monoclonal antibody (anti-BL4).

A monoclonal antibody (anti-BL4) recognizing a previously characterized Mr 54,000 glycoprotein (gp54) was developed by immunizing BALB/c mice with cells from a precursor B-cell line (Josh-7). In normal individuals, this antigenic molecule was present on tonsillar B-cells (60-80%) and on a fraction of peripheral blood B-cells (5-25%). BL4 (gp54) expression was investigated in 186 patients with a variety of hematological malignancies using indirect immunofluorescence and flow cytometric analysis. Twenty-six of 37 cases of B-cell chronic lymphocytic leukemia (CLL) and 18 of 33 cases of B-cell non-Hodgkin's lymphoma were BL4 positive. Surface expression of BL4 on reactive cases of CLL and non-Hodgkin's lymphoma was brighter than those of B1, B2, and B4, BL4 positive CLL cases expressed a higher proportion of mouse rosette forming cells and Leu-1 positive cells than the BL4 negative subgroup and were not associated with elevated serum immunoglobulin levels. Four of 7 BL4 negative CLL cases were associated with increased serum levels of immunoglobulin M. Lymphoblasts from 14 of 14 cases of non-T acute lymphoblastic leukemia and 3 of 3 pre-B lymphoid blast crisis of chronic myeloid leukemia were BL4 negative. Neoplastic cells from 2 of 3 cases of Waldenstrom's macroglobulinemia and 4 of 7 cases of hairy cell leukemia were BL4 reactive. None of 7 cases of multiple myeloma and plasma cell leukemia were BL4 positive. All 11 T acute lymphoblastic leukemia cases, 6 other T-cell malignancies, 5 cases of Hodgkin's disease, 51 cases of acute nonlymphocytic leukemia, and 9 cases of chronic myeloid leukemia in chronic phase thus far studied were BL4 negative. An in vitro induction experiment using phorbol ester on a case of B-CLL demonstrated disappearance of BL4 accompanied with further B-cell differentiation. Our study further substantiates the previous finding that gp54 is a differentiation antigen restricted to the B-cell lineage and expressed during the intermediate stage of B-cell ontogeny.

Animals↗

PubMed1986

Hairy cell leukemia: a model for studying the B cell family of diseases.

Nineteen patients with hairy cell leukemia (HCL) were treated with recombinant interferon alpha-2a/Roche (Roferon) given by daily intramuscular injection of 3 X 10(6) for 6 months followed by three injections per week. Pretreatment and follow-up marker studies were performed on 14 of 16 evaluable patients. Peripheral blood and bone marrow mononuclear cells were analyzed by flow cytometry for reactivity with monoclonal antibodies to B cell associated surface antigens (B1, B2, B4, BL1, BL3, and BL7) and two hairy cell (HC) antibodies, anti-HCL1 and HCL3. B cell monoclonality was determined by clonal excess calculation of immunoglobulin light chains. Right angle scatter analysis showed that HCs are scattered between lymphocytes and monocytes. Nine of the 14 patients achieved a partial remission, three patients achieved a minimal response, and two patients failed therapy. Phenotypically, ten patients had kappa clonal excess and four had lambda clonal excess. These cases expressed a mature B cell phenotype, ie, BL1-, BL7+, BL3+, B1+, B2-, B4+, HCL1+, HCL3+. All 12 responders became nonreactive with monoclonal antibodies 4 to 8 weeks after therapy; in five of these cases, reactivity with monoclonal antibodies was again detected at the time of maximum clinical response (2 to 8 months), without affecting clinical response status. In four of 12 responders, clonal excess disappeared 4 to 8 weeks after therapy; in three more patients, clonal excess disappeared at the time of maximum clinical response (2 to 4 months); in three patients, clonal excess disappeared from the peripheral blood, but not from the bone marrow at the time of maximum clinical response (3 to 5 months); two patients had persistent clonal excess. In the two failures, there was persistence of clonal excess and reactivity with monoclonal antibodies. This study shows that phenotypic analysis is a sensitive and objective method of assessing response of HCL to alpha interferon. This system could be used as a model for the study of other B cell neoplasms.

Adult↗

PubMed1985

Phenotypic analysis by flow cytometry of surface immunoglobulin light chains and B and T cell antigens in lymph nodes involved with non-Hodgkin's lymphoma.

The objective of this study was to demonstrate the diagnostic usefulness of flow cytometric analysis of surface membrane immunoglobulin light chain and monoclonal antibody reactivities in B cell non-Hodgkin's lymphoma. For this purpose, lymph node cell suspensions from 80 patients (20 normal lymph nodes, 11 lymph nodes with benign lymphoid hyperplasia, and 47 lymph nodes with B cell non-Hodgkin's lymphoma) were studied to detect the expression of surface B and T cell differentiation antigens recognized by a panel of monoclonal antibodies (anti-Leu-1, anti-Leu-5, anti-HLA-DR, J-5, anti-BL-1, anti-BL-2, and anti-BL-7). The clonal excess calculation, percent kappa-positive minus percent lambda-positive/percent kappa-positive plus percent lambda-positive cells per discrete level of fluorescence intensity, was used to study the clonality of surface membrane immunoglobulin light chain expression. Among the BL surface antigens, BL-7 proved to be most consistently expressed in B cell non-Hodgkin's lymphoma (79 percent). It was also present in 57 percent of lymph nodes with benign hyperplasia. No significant relationships were detected between the patterns of reactivity with the anti-BL monoclonal antibodies and histologic subtypes, although the small number of cases tested in each category precludes any definitive conclusions. Immunophenotypic heterogeneity within subgroups was also observed with expression of the other antigens examined. Monoclonal expression of surface membrane immunoglobulin light chain was seen in 43 of 47 (91 percent) of lymph nodes with non-Hodgkin's lymphoma, three of 11 (27 percent) hyperplastic lymph nodes, and one of 22 (4 percent) normal lymph nodes. When the presence of BL-7 and clonal excess was examined as a panel, 83 percent of B cell non-Hodgkin's lymphomas were positively identified, whereas one normal lymph node and no hyperplastic lymph nodes gave positive results. The simultaneous presence of clonal excess and BL-7 can be a useful diagnostic aid in the differentiation of lymphomatous from hyperplastic lymph nodes. Cytofluorimetry provides a rapid, objective, and reproducible technology to confirm the diagnosis of lymph node involvement in B cell non-Hodgkin's lymphoma.

Antibodies, Monoclonal↗

PubMed1985

Surface immunoglobulin light-chain expression by the "common" all cell line REH.

To provide further support of the B-cell lineage of "common" acute lymphoblastic leukemia (ALL), we studied the REH cell line and found not only cytoplasmic heavy chain but also surface lambda light-chain expression by flow cytometry. Nucleic acid blotting experiments on REH revealed that both kappa genes had been deleted and that lambda genes had been rearranged, as expected in B cells expressing lambda light chain. Moreover, REH cells contained mu and lambda RNA. When REH cells were treated with TPA the amount of mu chain RNA increased by approximately fivefold and the amount of lambda chain RNA increased by approximately twofold. The finding of surface immunoglobulin lambda light chain in the REH cell line, suggests that these leukemic cells are further differentiated along the B-cell lineage than was previously believed.

B-Lymphocytes↗

PubMed1985

Distribution of a new B-cell-associated surface antigen (BL7) detected by a monoclonal antibody in human leukemic disorders.

A murine monoclonal antibody (anti-BL7) was raised by immunization of BALB/c mice with a precursor B-cell line (Josh-7) which detects a heat-stable, nonimmunoprecipitable antigen. The expression of BL7 was investigated in peripheral blood and/or bone marrow leukemic cell suspensions stained by indirect immunofluorescence and analyzed by flow cytometry. Lymphoblasts from 43 of 43 cases of "null" acute lymphoblastic leukemia were BL7-. Five cases of T-acute lymphoblastic leukemia and 5 cases of terminal deoxynucleotidyl transferase-positive blastic chronic myelogenous leukemia were also BL7-. All 63 cases of B-cell chronic lymphocytic leukemia were BL7+. Neoplastic cells in 22 of 28 cases of B-cell non-Hodgkin's lymphomas in leukemic phase were also BL7+. Expression of BL7 showed some correlation with Rappaport's histological classification. Four cases of multiple myeloma and plasma cell leukemia were BL7-. Twenty-three cases of acute nonlymphocytic leukemias were also analyzed. Of these, only the acute promyelocytic (M3,4 cases) and acute myelomonocytic (M4, one case) varieties expressed BL7 on a small proportion (approximately 15%) of the leukemic cells. All other subgroups were BL7-. The reactivity of anti-BL7 was compared to other B-cell antibodies on selected samples and was shown to be different from B1, B2, and the BA antibodies. Anti-BL7 is a unique monoclonal antibody useful in the study of B-cell cancers.

Animals↗

PubMed1984

Treatment of diffuse poorly differentiated lymphocytic lymphoma. An analysis of prognostic variables.

Forty patients with diffuse poorly differentiated lymphocytic lymphoma (DPDL) Stages II-IV were treated with three different and successive combination chemotherapy protocols. Seventeen patients were treated with the cyclophosphamide (CTX) L2 protocol which included maintenance chemotherapy for 3 years. Only three patients were treated with the NHL-3 (non-Hodgkin's lymphoma) protocol, and 20 patients received the NHL-5 program. All protocols included radiotherapy (1500-4800 rad) to areas of initial bulky disease or persistent tumor, as well as central nervous system (CNS) prophylaxis with intrathecal methotrexate in patients with bone marrow involvement. Seventy-eight percent of local recurrences occurred in previously irradiated areas. Two-year survival rates were 55% and 70% for the CTX-L2 and NHL-5 protocols, respectively. Median disease-free survival for 24 complete response (CR) patients was 16.5 months. Of the 40 patients, 37 were evaluable for response to therapy. The CTX-L2 produced an 80% total response (TR) rate, a 60% CR, and a 20% partial response (PR). The patients on the NHL-5 achieved a TR rate of 95%, 74% CR, and 21% PR. Differences in TR and CR between the two protocols were not significant. Only 1 of 3 patients on the NHL-3 protocol achieved a CR. There was a trend for age greater than 50 years to lessen the chances of CR (P = 0.091); however, sex, symptoms, stage of disease, and LDH level were not significantly related to CR rate. Response to treatment (CR versus PR versus failure) was the most important factor influencing survival (P less than 0.001); age (greater than 50 years) was also significant (P = 0.008). Lactate dehydrogenase (LDH) was of borderline significance (P = 0.06). Cox regression model showed age (greater than 50 versus less than 50 years, P = 0.001), LDH (greater than 500 versus less than or equal to 500 U/L, P = 0.019) and symptoms (A or B) to be the best predictors of survival.

Adult↗

PubMed1984

Leu-10 (HLA-DC/DS) antigen distribution in human leukaemic disorders as detected by a monoclonal antibody: correlation with HLA-DR expression.

Reactivity of the monoclonal antibody anti-Leu-10 that detects the human equivalent of the murine 1-A subregion antigen(s) was studied and correlated with anti-HLA-DR expression on 83 cases of acute and chronic leukaemias, leukaemic non-Hodgkin's lymphomas (NHL) and seven human cell lines. Peripheral blood and/or bone marrow leukaemic cell suspensions were stained by indirect immunofluorescence for both monoclonal antibodies and analysed by flow cytometry. Leu-10, like HLA-DR, was absent from T-cell acute lymphoblastic leukaemia (ALL) (two cases). It was expressed on: 33% of TdT +, CALLA + ALL cases (8/24); 27% (4/15) of acute non-lymphocytic leukaemia (ANLL); 85% (24/28) of HLA-DR + B-cell chronic lymphocytic leukaemia (CLL); and on 9/14 (64%) B-cell NHL cases. There were no differences in clinical characteristics between Leu-10 + and Leu-10--patient subgroups. We were able to induce Leu-10 expression on 'Josh' cell line by culturing it with 12-0-tetra-decanoylphorbol-13-acetate (TPA). Our data indicate that Leu-10 expression on leukaemic cells is more restricted than HLA-DR and is likely to be differentiation related, since it can be induced to be expressed at a later stage than HLA-DR.

Adult↗

PubMed1984

Preparation and characterization of monoclonal antibodies recognizing two distinct differentiation antigens (Pro-Im1, Pro-Im2) on early hematopoietic cells.

A series of monoclonal antibodies recognizing myeloid differentiation antigens were prepared by immunizing Balb/c mice with HL-60 cells. Hybrids secreting antibodies reactive with HL-60 cells but unreactive with peripheral blood mononuclear cells were isolated and further cloned. One clone was found to produce an IgG2a antibody recognizing an 85,000-dalton molecular weight surface glycoprotein, and a second clone was found to produce an IgM antibody recognizing a heat-stable determinant present on a glycolipid. We have termed these antigens Pro-Im1 and Pro-Im2, respectively (Pro for using HL-60 promyelocytes as an immunogen and Im for the presence of these antigens on immature cells). alpha Pro-Im1 and alpha Pro-Im2 were used to investigate the surface expression and tissue distribution of these two antigens. Pro-Im1 and Pro-Im2 were found to be brightly expressed on a fraction of fetal liver hematopoietic and bone marrow cells. Both antibodies mediated complement-dependent inhibition of CFU-GM, BFU-E, and CFU-GEMM formation assayed by soft agar colony and burst formation, indicating the expression of these antigens by early hematopoietic precursor cells. This was further confirmed by the induction of HL-60 cells by TPA to differentiate into more mature monocytes and macrophages, accompanied by the loss of both antigens. Pro-Im1 and Pro-Im2 were absent from peripheral blood monocytes, erythrocytes, and platelets, but Pro-Im2 was expressed on granulocytes. Both antigens were absent from thymocytes and peripheral T cells. Cytofluorographic analysis suggested their absence from peripheral blood B cells but that both were expressed on a minority of tissue B cells. Analysis of 150 cases of various myeloid and lymphoid malignancies demonstrated Pro-Im1 and Pro-Im2 expression on myeloblasts and promyelocytes from some acute myelogenous leukemias as well as some B cell malignancies, suggesting that these antigens are shared by early hematopoietic cells and a subset of B cells.

Animals↗

PubMed1984

Preparation and characterization of monoclonal antibodies recognizing three distinct differentiation antigens (BL1, BL2, BL3) on human B lymphocytes.

We report in this paper the generation and characterization of three monoclonal antibodies, designated alpha BL1, alpha BL2, and alpha BL3, that recognize distinctive antigens unrelated to complement, Fc, and mouse erythrocyte rosette receptors, which are preferentially expressed on B lymphocytes. alpha BL1 recognizes a heat stable nonimmunoprecipitable antigen, possibly glycolipid in nature. Alpha BL2 recognizes a nonreducible single polypeptide with a m.w. of 68,000 that occasionally co-precipitates with a p29,34 complex of HLA-DR antigens. Alpha BL3 recognizes a nonreducible single polypeptide with a m.w. of 105,000 with an acidic pI point. We demonstrated that BL1 is expressed on fetal liver hematopoietic cells, a small subset (5 to 15%) of Ficoll-Hypaque-separated normal bone marrow cells, and on a subpopulation of nonadherent, non-E rosette-forming cells and granulocytes. BL2 is expressed on fetal liver hematopoietic cells, on 3 to 7% of normal bone marrow cells, and on a majority (40 to 70%) of nonadherent, non-E rosette-forming cells with a distinctive pattern similar to that of HLA-DR. BL3 is expressed on a subpopulation of nonadherent, non-E rosette-forming cells, and on occasional cells in the monocyte-enriched adherent cell population. The peak fluorescence for BL2 is substantially higher than that of BL1 and BL3, indicating higher BL2 antigen density. All three antigens are absent from thymocytes and E rosette-positive T cell fractions obtained from various lymphoid tissues. Cellular distribution of the BL antigens on various well-characterized established hematopoietic cell lines, leukemias, and malignant lymphomas, in conjunction with the results of the in vitro activation and TPA-induction experiments, suggest that BL1 is expressed during early developmental stages of B cell differentiation, whereas BL3 is expressed at the later stages. BL2 expression spans immature and mature stages of B cell differentiation, with the exception of mature plasma cells. The alpha BL antibodies described here should prove to be useful in the investigation of B cell differentiation and in the clinical diagnosis of lymphoid neoplasms.

Animals↗

PubMed1983

Induction of HLA-DC/DS (LEU 10) antigen expression by human precursor B cell lines.

The expression of HLA-DC/DS antigen detected by the monoclonal antibody Leu 10 was studied in three human precursor and pre-B cell lines (Josh 7, Reh, and Nalm 12). Flow cytometric analysis showed that none of these cell lines stained for the HLA-DC/DS antigen. In the presence of 1.6 X 10(-9) M of 12-O-tetradecanoylporbol-13-acetate (TPA), expression of this antigen was detected. The expression was completed after 168 h of incubation. Iodination of cell surface, immunoprecipitation by Leu 10 antibody, and two-dimensional gel analysis revealed that TPA-treated Josh 7 cells synthesized and expressed a 29,34 kD bimolecular complex with both alpha and beta chains different from those of HLA-DR antigen. Quantitative absorption experiments with cell lysates indicated a greater than 25-fold increase in HLA-DC/DS antigen in TPA-treated cells. With the induction of HLA-DC/DS antigen expression, there are concomitant decreases in the expression of the common acute lymphoblastic leukemia antigen (CALLA) and the enzymatic activity of terminal deoxynucleotidyl transferase. No appreciable changes in HLA-DR and Ig expression were observed. There was also no change in HLA-SB expression as detected by antibody ILR-1. However, DNA synthesis was markedly inhibited by TPA treatment. These results indicate that precursor and pre-B cell lines can be induced to mature in vitro. They also suggest that the expression of HLA-DC/DS antigen which precedes the expression of membrane Ig and follows the HLA-DR expression is relevant to human B cell development and cell interaction.

Agammaglobulinemia↗

PubMedDate not supplied

Phenotypic characterization of 'non-T, non-B' acute lymphoblastic leukemia by a new panel (BL) of monoclonal antibodies.

Peripheral blood and/or bone marrow leukemic cell suspensions from 49 patients with 'non-T, non-B' acute lymphoblastic leukemia (ALL) were analysed by flow cytometry using a new panel of four monoclonal antibodies. Anti-BL1 and anti-BL2 originating from NALM-6 and B35M lymphoblastoid cell lines, respectively. These antibodies recognize B-cell differentiation antigens: a heat stable non-immunoprecipitable antigenic determinant, and a 68 000 daltons glycoprotein molecule, respectively. BL5 and BL6 were derived by immunization with the promyelocytic cell line HL-60, recognizing antigens present on early hematopoietic cells: an 85 000 daltons MW glycoprotein (Pro-Im 1) and a heat stable antigen (Pro-Im2), respectively. All ALL patients studied had L1 or L2 morphology by the FAB classification and a blast count exceeding 50 per cent. There were 25 males and 24 females. Median age was 8 years (range 1-67 years). Thirty-nine cases were studied at initial presentation and 10 at relapse. Cells from 46/49 cases expressed BL2 and/or BL1, but were not reactive with BL5 or BL6. Three of 49 cases did not express BL1 or BL2. However, a small percentage of blasts from one case was positive for BL5 (13 per cent) and the other 2 cases were reactive with BL6 (20 per cent and 36 per cent, respectively). These were one adult and 2 pediatric patients that had other ALL markers and achieved a complete remission with appropriate ALL therapy. One of the BL6+ cases relapsed after 19 months with a change in phenotype to BL1+ BL2+ BL5- BL6-. This analysis shows that the majority of 'non-T, non-B' ALL's do express B-cell associated antigens (BL1/BL2) argumentative of their B-cell origin. A small subgroup does not express such antigens and may arise from a more immature cell, since they expressed antigens on early hematopoietic stem cells.

Adolescent↗