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T Robak

Publications and source records attributed to T Robak.

At least 199 records · Page 11Linked to original sources
PubMed1988

Antigenic phenotype of chronic granulocytic leukaemia progenitor cells in chronic phase and in blastic transformation characterized by means of monoclonal antibodies.

We studied the surface antigens of "early" and "late" granulocyte-macrophage progenitor cells (CFU-GM) from bone marrow and peripheral blood of 18 patients with chronic granulocytic leukaemia in chronic phase (CGL-CP) using 14 selected murine monoclonal antibodies (McAbs) in complement dependent cytotoxicity assay followed by culture in methyl cellulose. The same panel of McAbs was used to determine the antigens on leukaemic blast cells from peripheral blood of 15 patients with CGL in blastic transformation (BT) by complement mediated lysis and in vitro culture technique for clonogenic blasts (CFU-L) and immunofluorescence assay for total blast population. McAb for HLA-DR antigens (L243) and McAbs MY9, S3-13, S17-25 and 53/6 reacted with CFV-GM and CFU-L. In contrast, McAbs PM81 and AML-2-23 recognizing antigens on more mature myeloid cells did not react with these progenitor cells. McAb S4-7 reacted with the majority of CFU-L and a small proportion of "early" and "late" CFU-GM. This McAb may be useful for the prediction of blastic transformation in CGL patients. Generally, the reactivity of most McAbs was more heterogeneous with CFU-L than with CFU-GM in individual patients. The majority of McAbs included in our study reacted with a higher percentage of CFU-L and CFU-GM than predominant blast cell population in individual patients perhaps because the detected antigens are expressed more strongly on dividing progenitors than on relatively nonproliferative progeny. Thus we interpret the results of these studies showing that the antigenic phenotypes of the blast colony progenitor cells in CGL-BT are very similar to but not identical with those of CFU-GM from CGL-CP patients.

Adolescent↗
PubMed1988

Application of monoclonal antibodies in the antigenic characteristics of normal myeloid progenitor cells and clonogenic blasts in acute myeloid leukaemia.

The antigenic characteristics of "early" and "late" granulocyte-macrophage progenitor cells (CFU-GM) from normal bone marrow (NBM) and normal peripheral blood (NPB) were studied using 14 selected murine monoclonal antibodies (McAbs) in a complement dependent cytotoxicity assay followed by culture in methyl cellulose. The same panel of McAbs was used to determine the antigens on leukaemic colony-forming cells (CFU-L) from the blood of 14 patients with acute myeloid leukaemia (AML). McAbs L243 (anti-HLA-DR antigen), MY9, S3-13 and S17-25 were cytotoxic almost completely with CFU-GM from NBM as well as from NPB, McAbs R1, B19 and WGHS 29.1 reacted with a high percentage of NBM CFU-GM but not with those from NPB. The antigens expressed on normal CFU-GM were also found on the CFU-L in the majority of patients. However, PMN29 reacted strongly with "late" CFU-GM from NBM and did not react with CFU-L. In contrast, some of the McAbs (S4-7, VIM-2) recognized the antigens on a much higher proportion of CFU-L than "early" CFU-GM from NBM. The expression of the majority of the antigens on leukaemic clonogenic cells tends to vary between different patients and also between the different cells of an individual patient. We conclude that some of the McAbs could be used in the further investigations for their usefulness in the treatment of selected patients with AML, for example in the immunoseparation of leukaemic stem cells of an individual patient.

Adolescent↗
PubMed1988

Antigenic characteristics of erythropoietin dependent and independent erythroid progenitors (BFU-E and CFU-E) in polycythaemia vera and idiopathic myelofibrosis defined by monoclonal antibodies.

The antigenic characteristics of erythropoietin (Ep) dependent and independent ("endogenous") erythroid progenitor cells (BFU-E and CFU-E) from patients with polycythaemia vera (PV) and idiopathic myelofibrosis (MF) were studied using 9 selected murine monoclonal antibodies (McAbs) in a complement dependent cytotoxicity assay followed by culture in methyl cellulose. McAbs L343 (HLA-DR antigen) S3-13 and S17-25 reacted with about 50% of BFU-E in MF and PV. In contrast HLA-DR antigens were not presented on CFU-E. McAbs R1.B19, WHGS29.1, PMN29 and PM81 recognized the antigens on less than 25% of BFU-E and CFU-E. The reactivity of Ep-dependent and Ep-independent BFU-E and CFU-E was similar with the majority of McAbs. However, McAbs S4-7 and VIM-2 reacted with a higher proportion of Ep-independent BFU-E than of Ep-dependent BFU-E. These results indicate that Ep independent, neoplastic BFU-E in PV and MF are more mature than their Ep dependent counterparts. The antigens expressed on erythroid progenitor cells from patients with PV and MF were earlier found on BFU-E and CFU-E from normal bone marrow and peripheral blood, usually on a higher proportion of cells, than in myeloproliferative disorders.

Aged↗
PubMed1987

Antigenic phenotype of the myeloid leukaemic cells defined by monoclonal antibodies.

The antigenic characteristics of the leukaemic cell population in 31 patients with acute myeloid leukaemia (AML) and 5 patients with acute undifferentiated leukaemia (AUL) was investigated using a panel of 15 monoclonal antibodies (Mc Abs). We chose 14 Mc Abs that react with lineage--and stage related myeloid antigens and L243 Mc Ab that reacts with HLA-DR antigen. In AML cases we correlated the antigenic phenotype with morphological FAB classification. The study indicates a substantial antigenic heterogeneity of the surface antigen expression on leukaemia cells particularly in M1, M2 and M4 AML cases. The morphological subtype of these leukaemias tended to correlate with the immunologic phenotype, particularly in more differentiated AML cases such as M3 or M5. The most immature cell phenotype characterised "undifferentiated" AML, which was expressed by the reactivity or L243, BI3C5, MY9, VIM-2 and S3-13 Mc Abs with the majority of the patients. The analysis shows that although there is a tendency for the morphology to correlate with the surface antigen phenotype each morphological group contains patients having different surface antigen phenotype.

Acute Disease↗
PubMed1987

Expression of myeloid differentiation antigens on normal and chronic granulocytic leukemia erythroid progenitor cells identified by monoclonal antibodies.

The antigenic phenotype of erythroid progenitor cells (BFU-E and CFU-E) in bone marrow and peripheral blood from normal individuals and patients with chronic granulocytic leukaemia (CGL) was studied using 14 myeloid monoclonal antibodies (Mc Abs) in a complement dependent cytotoxicity assay followed by culture in methylcellulose. Mc Abs which reacted with normal CFU-GEMM and CFU-GM antigens usually reacted strongly with normal and CGL-BFU-E. In contrast, the majority of myeloid Mc Abs used in the study reacted poorly or did not recognize the antigens on normal and CGL CFU-E. HLA-DR antigens recognized by L243 Mc Ab were expressed on the majority of BFU-E from blood and bone marrow of normal individuals and CGL patients. On the other hand, those antigens were not expressed on normal and leukaemic CFU-E. Two Mc Abs, R1.B19 and WGHS29.1, which recognised the antigens on "late" CFU-GM and not on "early" CFU-GM reacted with a higher proportion of BFU-E from the marrow and blood of CGL patients than of normal subjects. These results indicate that BFU-E in CGL are more differentiated than their normal counterparts. The Mc Ab 54/39, frequently expressed on platelets, recognized a higher percentage of BFU-E and CFU-E from CGL patients than from normal individuals. This may suggest that in CGL there exists a tendency for the expression of megakaryocytic markers on erythroid progenitor cells.

Antibodies, Monoclonal↗
PubMed1986

Antigenic determinants on myeloid leukaemia colony-forming cells resemble those of normal myeloid progenitor cells and differ from those of circulating blast cells.

We studied the antigenic characteristics of leukaemic colony-forming cells (CFU-L) from the blood of patients with chronic granulocytic leukaemia (CGL) in blastic transformation (BT) and acute myeloid leukaemia (AML) by in vitro culture techniques after complement-mediated lysis with one anti-DR and 10 selected myeloid monoclonal antibodies (McAbs), all of which were cytotoxic in the presence of complement. At the same time we studied the antigenic characteristics of the circulating blast cells from the same patients using in addition one non-complement fixing antibody (BI.3C5) with standard immunofluorescence and immunoalkaline phosphatase techniques. We also used myeloid progenitor cell assays in conjunction with cytotoxic McAbs to investigate the antigenic determinants on Day 7 CFU-GM, Day 14 CFU-GM and BFU-E from the blood of patients with CGL in chronic phase (CP) and from normal bone marrow. We found that two of the McAbs, S4-7 and WGHS29.1, recognized a higher proportion of CFU-L from the blood of AML patients than from patients with CGL-BT. However, the patterns of reactivity for CFU-L from CGL-BT and AML patients with the other McAbs quite closely resembled those observed in CFU-GM and BFU-E from normal individuals and patients with CGL in CP. A McAb with DR specificity and one of the myeloid McAbs, 54/39, recognized both CFU-L from CGL-BT and AML and reacted also with circulating blast cells from the same patients. In contrast, six of the other myeloid McAbs that recognized CFU-L failed to label the corresponding blast cells. We conclude that the antigenic properties of CFU-L in CGL-BT and AML are very similar to, but perhaps not identical with, those of normal CFU-GM and BFU-E. There was a major discrepancy in the antigenic profiles of CFU-L and of the blast cells predominating in the blood.

Antibodies, Monoclonal↗
PubMed1986

Staging of leukemic progenitor cells in acute myeloid leukemia by phenotyping with myeloid monoclonal antibodies.

We studied the immune phenotype of leukemic progenitor cells (AML-CFU-L) in 16 cases of acute myeloid leukemia (AML) using 12 myeloid monoclonal antibodies (McAbs) in a complement-mediated cytotoxicity assay. On the basis of their reactivities with normal day-14 (D14) and day-7 (D7) myeloid progenitor cells (CFU-GM), these McAbs could be classified into three groups: six McAbs reacted strongly with "early" antigens on D14-CFU-GM, two McAbs reacted only with "late" antigens on D7-CFU-GM, while four McAbs formed an "intermediate" group that reacted both with the "late" antigens on D7-CFU-GM and to some extent with the "early" antigens of D14-CFU-GM. The McAbs all reacted with antigens on AML-CFU-L:McAbs that reacted with "early" antigens reacted consistently strongly with AML-CFU-L, in contrast to McAbs in the two other groups, which displayed greater heterogeneity. On the basis of antigenic phenotype, the predominating CFU-L in AML could thus be placed in one of three "stages." This phenotypic "staging" of AML correlated with the French-American-British (FAB) morphological classification of AML. The AML-CFU-L of patients with FAB morphological types M2, M4, and M5 expressed more differentiated antigenic phenotypes than those of the three patients with M7. The latter reacted poorly with the "intermediate" and "late" McAbs. Our data and those of others suggest that classification based on AML-CFU-L antigenic profile may complement the FAB classification of AML.

Adolescent↗
PubMed1986

Endogenous erythroid colony formation in myeloproliferative diseases does not depend on T cells.

We investigated the influence of T-cell depletion on BFU-E and CFU-GM colony growth in vitro from normal individuals and patients with chronic granulocytic leukemia (CGL), idiopathic myelofibrosis (MF), and polycythemia vera (PV). Preincubation of mononuclear cells with the complement-fixing monoclonal antibody OKT11A, which is cytotoxic to T-lymphocytes, significantly reduced the number of erythropoietin (epo)-dependent BFU-E colonies cultured from normal bone marrow and normal peripheral blood, as well as from the blood of patients with CGL, PV, and MF. In contrast, the numbers of epo-independent ("endogenous") BFU-E colonies cultured from the blood of PV and MF patients were the same before and after T-cell depletion. The blood and marrow of CGL patients and normal individuals produced no epo-independent BFU-E proliferation. The growth of day-7 and day-14 CFU-GM was not significantly influenced by T-cell depletion in the majority of experiments. We conclude that T cells promote the growth of epo-dependent BFU-E colonies in vitro, but they do not influence the growth of "endogenous" BFU-E colonies from patients with myeloproliferative disorders.

Adult↗
PubMed1985

Antigenic characteristics of circulating CFU-GM in chronic granulocytic leukaemia resemble those of CFU-GM in normal marrow and differ from those in normal blood.

We studied the surface antigenic determinants of myeloid progenitor cells (Day 7 CFU-GM, Day 14 CFU-GM and BFU-E) in the peripheral blood and bone marrow of patients with chronic granulocytic leukaemia (CGL) and normal subjects by complement-mediated cytotoxicity with a panel of 8 selected murine monoclonal antibodies (McAbs) followed by culture in methyl cellulose. All classes of progenitor cell studied expressed HLA-DR antigens and also expressed other antigens recognized by two of the McAbs (S3-13 and S17-25) with myeloid specificity. Two other McAbs (R1.B19 and WGHS.29.1). Recognized antigens on Day 14 CFU-GM derived from normal marrow but not on those from normal blood. The pattern of reactivity of Day 14 CFU-GM from the blood of patients with CGL resembled to a considerable extent that of CFU-GM from normal marrow and differed from that of CFU-GM from normal blood. BFU-E from the blood of patients with CGL reacted with these McAbs in a manner very similar to that of BFU-E from normal blood; however the same two McAbs (R1.B19 and WGHS.19.1) reacted with a much higher proportion of the BFU-E from the marrows of CGL patients than of normal subjects. Our data are consistent with the hypothesis that normal blood-derived CFU-GM are more primitive than marrow-derived CFU-GM; however the CFU-GM in the circulation in CGL differ from those in normal blood, perhaps because they reflect overflow from or exchange with a hyperplastic marrow population.

Animals↗