Masking of neutrophil surface lectin-binding sites in chronic myelogenous leukemia (CML).
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Biomedical subjects
Publications and source records attributed to R N Taub.
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Blast cells were obtained from 17 patients with acute undifferentiated leukemia and 13 patients with chronic myelogenous leukemia in blast crisis. The blasts were tested with anti-i serum in cytotoxicity tests and with antisera to myeloblastic leukemia-associated antigens in immunofluorescence tests. The terminal deoxynucleotidyl transferase (TDT) content of the blasts was also measured. Lymphoblasts react strongly with anti-i, do not react with anti-myeloblast serum, and have high levels of TDT; myeloblasts react weakly with anti-i, do not react with anti-myeloblast serum, and have very low levels of TDT. Of the 17 patients with acute undifferentiated leukemia, there were six with blasts which reacted like lymphoblasts, six with blasts which reacted like myeloblasts, and five with blasts bearing different combinations of these lymphoblastic and myeloblastic markers. Eight of the 11 patients with lymphoblastic or mixed lymphoblastic-myeloblastic markers, but only one of the six with myeloblastic markers, achieved complete or partial remission in response to therapy. Thus, in acute undifferentiated leukemia, classification of blasts with these markers may be of prognostic value. Of the 13 patients with chronic myelogenous leukemia in blast crises, the markers were concordant (for myeloblasts) in only two cases. Three of the 13 patients had TDT-positive blasts, but the reactions of these cells with anti-i and with anti-myeloblast serum differed from those seen with lymphoblasts from patients with acute lymphoblastic leukemia. Although the cell involved in "lymphoid" blast crisis of chronic myelogenous leukemia is similar in many respects to that involved in acute lymphoblastic leukemia, these cells are not identical.
We have raised a monkey antiserum that is selectively reactive with human leukemic myeloblasts by immunization with a glycoprotein antigen (AMLSGA) released from myeloblasts in short-term culture. Antimyeloblast activity can be demonstrated using complement-dependent cytotoxicity or indirect immunofluorescence. Selective antimyeloblast activity is retained following absorption with leukemic lymphoblasts or lymphocytes, nonleukemic lymphocytes, neutrophils, or mononuclear cells from nonleukemic bone marrow. Anti-AMLSGA antisera are not reactive with B-cell-enriched cell populations, and antaimyeloblast activity is not reduced by absorption with Ia-positive cells. Anti-AMLSGA is a useful reagent for identification of human leukemic myeloblasts.
We tested serial bone-marrow samples from 47 adults with acute myeloblastic leukemia in remission for reactivity with heteroantiserums to leukemia-associated antigens, to determine whether imminent relapse could be detected in patients with acute leukemia. Of 26 patients who relapsed by standard morphologic criteria, 21 had increased immunoreactivity of bone marrow for one to six months (mean, 3.7 months) before relapse. High concordance was observed between a positive test and relapse during the period of study (chi-square = 27.53, P less than 0.001). The median time to relapse after a positive test was four months, as compared with the median remission duration of 19 months for the whole group (P less than 0.02, Peto's log-rank analysis). Serologic detection of leukemia-associated antigens in marrow may be a reliable indicator of imminent relapse in acute myeloblastic leukemia.
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To evaluate the pathogenetic significance of impaired cellular immunity in inflammatory bowel disease (IBD), we have measured the cutaneous responsiveness to dinitrochlorobenzene (DNCB) among 58 patients with IBD, 33 with Crohn's disease and 25 with ulcerative colitis, 63 of their clinically normal relatives, 24 additional ileitis and colitis patients who had undergone resection of all visibly diseased bowel, and 23 control subjects. Cutaneous anergy to DNCB was demonstrated among 70% of the patients with CD and 48% of those with UC, as against only 9% of the controls (p less than 0.001). There was no increased incidence of anergy among either 44 first-degree relatives (7%) or 19 spouses (3%), nor was there any special proclivity toward anergy among six pairs of patients with familial inflammatory bowel disease. In Crohn's disease, anergy was still present after bowel resection in six of 10 patients (60%), while in ulcerative colitis anergy was found after colectomy in only two of 14 patients (14%). Our data suggest that the immune defect in patients with inflammatory bowel disease may be a secondary phenomenon. In ulcerative colitis, the defect appears to reverse after colectomy, but in Crohn's disease it persists despite resection. This finding is consistent with the observed tendency of Crohn's disease, but not ulcerative colitis, to inexorable postoperative recurrence.
Three preparations of BCG, currently in use for clinical trials in cancer, were tested for relative potency as an immunological adjuvant. Using a lymphocyte trapping assay, Pasteur Institute BCG was shown to be a more effective adjuvant than the Tice strain or the Glaxo preparation of BCG.
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Peripheral blood myeloblasts from five patients with acute myeloblastic leukemia and peripheral remission leukocytes from two of these patients were radiolabeled by the lactoperoxidase-catalyzed surface radioiodination technique and incubated in a nutrient medium at 37 degrees. Radioactive materials shed from viable cells into the supernatant at 24 hr were purified by gel filtration and by DEAE-cellulose chromatography. The radiolabeled leukemic cells shed relatively few molecular species into the culture medium. The DEAE-cellulose eluate usually contained one major peak in which radioactivity and protein levels were coincident; the molecular weight of this compound was 350,000 to 400,000, and it contained carbohydrate as well as protein. Glycoprotein shed from leukemic cells was specifically reactive in a coprecipitation assay with defined antimyeloblast alloantisera obtained from leukemic patients receiving immunotherapy. No reaction was seen with antisera directed against HLA or B-cell antigens. Material shed from remission cells did not coprecipitate with antileukemic antisera. The isolation of radioactively labeled antigen derived from myeloblasts may ultimately allow the monitoring of human antigen levels in leukemic blood by radioimmunoassay.
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Specific immunological hyporeactivity to Ag-B incompatible rat renal allografts was achieved after pretreatment of the recipients with donor strain platelets or spleen cells and cyclophosphamide (CY). The longest survival times were observed in animals pretreated with a single 75 mg/kg dose of CY together with 2 X 10(10) donor strain platelets or 2.5 X 10(9) spleen cells intravenously, 2 weeks prior to kidney transplant (median survival time, 71 and 47 days, respectively, compared to 12 days in untreated rats). CY or antigen given alone were ineffective. Anti-donor antibody activiy was routinely detectable in graft-bearing animals. Cell-mediated anti-donor immunity, although impaired, was still present in long-term survivors. These findings suggest that preservation of graft function and prolonged survival in antigen-CY-pretreated animals may be abetted by a combination of mechanisms including antigen-induced immunological enhancement, and deletion by CY of potentially reactive lymphoid cell clones. The use of CY in conjunction with donor antigen pretreatment may provide an additional increment of specific immunosuppression in clinical organ transplantation.
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The laboratory rat has been widely used as a preclinical model of renal transplantation. Surgical anastomosis of the small lumenal structures encountered requires strict adherence to basic principles of microsurgical technique. Nonfatal technical errors may adversely affect renal allograft function and influence experimental results. Experience obtained from a series of more than 600 rat renal transplants is discussed.
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A method is described for raising antisera to human leukemia cells of an individual patient in mice rendered tolerant with cyclophosphamide to platelets obtained from the same patient. The resulting antisera are able to distinguish serologically between leukemic blast cells and remission cells of patients with acute leukemia and may be recognizing leukemia-associated antigens. The antisera are similar in activity to antisera raised following tolerance-induction with remission leukocytes, but larger volumes of anti-leukemia antiserum can be raised using the more easily obtainable platelets. This technique provides further evidence that human platelets share many of the antigens present on human leukocytes.
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