Surface Ia-like expression and MLR-stimulating capacity of human leukemic myeloblasts: implications for immunotherapy and prognosis

Surface Ia-positive cells were found to vary from 0 to 100% in initial blood specimens from 37 adults with acute myelogenous leukemia (AML). When myeloblasts from 19 patients were tested against panels of lymphocytes from 5 to 19 normal donors, mean stimulation indices ranged from 1 to 60. Some leukemic myeloblasts strongly stimulated most allogenic responder lymphocytes whereas others produced almost no stimulation. The addition of antibody against human Ia to 28 mixed leukocyte reaction (MLR) combinations resulted in significant inhibition (p less than 0.001) of 3H-thymidine incorporation. Testing of myeloblastic Ia may have clinical relevance because patients with greater than 50% Ia-positive myeloblasts had a significantly longer survival than patients with fewer Ia-positive myeloblasts (p less than 0.04).     

Interleukin-2 can induce proliferation of leukemic B-cells in prolymphocytic leukemia

In a case of prolymphocytic leukemia (PLL), receptors for interleukin-2 (IL-2R) were demonstrated by immunofluorescence with a monoclonal antibody against IL-2R. Highly purified leukemic B-cells, cultured in vitro with recombinant IL-2 (r-IL-2), responded to IL-2 with a marked increase of DNA-synthesis. Both spontaneous and r-IL-2-induced proliferation of leukemic cells were totally abrogated by the anti-IL-2R monoclonal antibody.     

Iron, free radicals and cancer.

Free radicals, intermediates in the tissue damage caused by radiation, are formed, inter alia, in interactions catalyzed by iron, which synergizes with radiation and some cytostatics (anthracyclins) in causing cell damage. Conversely, iron chelators can counteract cell damage. Similarly, antioxidants can slow atherogenesis, caused in part by oxidative stress and free radicals. Cell damage is also prevented by physiological defense systems like superoxide dismutase, against endogenous free radicals formed by granulocytes, monocytes, etc. Iron can thus induce free radicals which cause DNA double strand breaks and oncogene activation. This is suggested by four epidemiological studies suggesting a higher cancer risk in patients with larger iron stores than in those with small iron stores. In addition to its effect on carcinogenesis, iron can also maintain the growth of malignant cells as well as growth of pathogens. Breast cancer cells, for instance, display 5-15 times more transferrin receptors than normal breast tissue. Iron-carrying transferrin is in fact a growth factor. Hyposideremia in patients with cancer or infection is not a paraphenomenon but a functioning defense mechanism ('nutritional immunity'). If this immunity is broken by iron administration, relapses of diseases like tuberculosis, brucellosis, and malaria have been described. While iron-deficiency anemia should of course be diagnosed, treated and if possible prevented, there are good reasons to avoid over-utilization of medicamental iron.     

Studies in dumping syndrome

In 310 patients with tuberculosis—38 of whom had been subjected to partial gastrectomy because of duodenal or gastric ulcers—46 social, clinical, and laboratory parameters were recorded, and a correlation matrix consisting of 11,000 correlations between them was calculated. Results showed that tuberculosis occurred significantly more often and that it was more widely extended in gastrectomized patients with dumping syndrome than in patients with normal stomachs. The lower the intestinal absorptions and serum concentrations of nutrients, the more bacilli were found in the sputum, and the more frequently tuberculous relapses occurred in such patients. In addition, the worse the social conditions, the earlier the onset of tuberculosis, and the greater its extent. In Stockholm, the typical tuberculosis patient is an alcoholic, divorced, poorly housed, gastrectomized man. Patients with poorer initial social and medical conditions proved more amenable to treatment in terms of increasing weight, reducing erythrocyte sedimentation rate, and improving leucocyte response. On the other hand, the more often the patient is hospitalized with a relapse, the more resistant bacilli become to chemotherapy (or vice versa), causing poor response to treatment, greater extent of disease, and higher mortality. The fact that tuberculosis is frequent among the gastrectomized and the socially indigent, and that it is amenable to treatment in them, motivates the attempt to initiate systematic controls and perhaps even prophylactic treatment.Supported by the Swedish Association Against Heart and Chest Diseases and the Ekhaga foundation.A preliminary report was presented in a symposium at the Swedish Medical Association National Conference on Dec 1, 1967.