Human leukemic cells: Biological action of exogenous human leukemic DNA

Intact exogenous human leukemie DNA derived from cells in culture was taken up by both normal and leukemic recipient human cells, wherein it migrates to the nucleus and becomes associated with host genome. Uptake of exogenous DNA averages about 15–20 percent and was relatively higher in leukemic than in normal cells in a given culture medium.Isologous and homologous human leukemic cells were more sensitive to inhibition by this exogenous DNA than were normal human cells. Both DNA and RNA synthesis were inhibited, but protein synthesis was stimulated — effects similar to those described consequent to exposure to certain viruses.Immunological studies of hamster cells treated with human leukemic DNA failed to show any presence of human surface antigens. The in vivo studies showed that this metabolically active radioactive DNA had migrated to several organs of hamsters and gerbils, the highest labeled DNA activity being found in the testis and kidney of these animals.Prolonged exposure to exogenous leukemic DNA resulted in marked phenotypic changes in normal human fibroblasts, which thus far appear to be heritable. Search for evidence of genotypic changes in these altered cells which might relate these observations to «neoplastic transformation is in progress.     

Cytology of leukemic lymphadenopathy

OBJECTIVE: To describe the cytomorphologic features of leukemic cells in lymph node aspiration material. STUDY DESIGN: We studied lymph node fine needle aspiration (FNA) smears of 36 leukemic patients. In 23 cases the lymphadenopathy was noticed simultaneously with marrow leukemia, and in the other 13 cases the lymphadenopathy was noticed during a relapse. Special stains, such as periodic acid Schiff, Sudan Black-B, Oil Red-O and nonspecific esterase, were used in special cases. RESULTS: Thirty-three cases were diagnosed as lymphoma, 1 as extramedullary hematopoiesis and 2 as leukemic involvement. CONCLUSION: Leukemic lymphadenopathy can be misdiagnosed as lymphoma on FNA smears. The clinical findings, previous history, hematologic studies and immunocytochemical studies are essential to the differentiation of leukemic smears from lymphoma. However, in some cases the leukemic infiltration can be diagnosed with certainty, provided that the smears show the characteristic findings, such as Auer rods and neoplastic promyelocytes with azurophilic granules.     

Magnesium contents of leukemic lymphocytes

In this study, magnesium concentrations were measured in lymphocytes from patients with acute myeloblastic leukemia (AML), chronic megalositer leukemia (KML) and acute lymphoblastic leukemia (ALL) before and after chemotherapy management, and results were compared with those of control subjects. Magnesium concentrations were higher in the patient groups compared with control values. However, no meaningful differences were found among magnesium concentrations of the patient groups themselves. Similarly, no statistically meaningful differences were found between lymphocyte magnesium concentrations before and after chemotherapy management in the patient groups. In the inter-correlation analysis, we observed no correlations between pre- and post-magnesium concentrations in patients' lymphocytes. It has been suggested that magnesium concentrations of leukemic lymphocytes might increase due to the high ATP requirement of the leukemic cells since magnesium is known to play an important part as a cofactor in most of the energy-producing reactions.     

Complement activity in leukemic patients]

The in vitro test of heterologous anti-leukaemic sera against human leukaemic cells resulted in the serum of leukaemic patients being able to produce a lysis of leukaemic cells in the leukaemic phase as well as in remission when specific heterologous antibodies were present.     

ATRA promotes alpha tocopherol succinate-induced apoptosis in freshly isolated leukemic cells from chronic myeloid leukemic patients

We investigated the in vitro efficacy of all-trans retinoic acid (ATRA) and alpha-tocopherol succinate (α-TS) alone and in combination on the induction of cell death in freshly isolated leukemic cells obtained from chronic myeloid leukemia (CML) patients. In vitro cytotoxicity and induction of lipid peroxidation by ATRA (10 μM) and α-TS (25 or 50 μM) were evaluated in primary leukemic cells by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and malondialdehyde formation respectively. Treatment of leukemic cells with α-TS alone or in combination with ATRA significantly (P < 0.05) decreased the cell viability in a concentration and time dependent manner as compared to peripheral blood mononuclear cells obtained from normal healthy controls. Lipid peroxidation was enhanced by 98% (P < 0.05) on combined treatment of cells with ATRA (10 μM) and α-TS (50 μM). ATRA alone did not enhance the externalization of phosphatidyl serine as studied by annexin-V binding using fluorescence activated cell sorter analysis, whereas in combination with α-TS it increased to 400% at 12 h. The treatment of leukemic cells to combination of ATRA with α-TS significantly decreased (P < 0.05) mitochondrial membrane potential and enhanced lysosomal destabilization. The combination of these drugs also increased mitochondrial and cytosolic reactive oxygen species (ROS) production, nitric oxide levels, and caspase-3 activity significantly and caused DNA fragmentation at 24 h in a concentration dependent manner in the leukemic cells. Our data suggest that ATRA in combination with α-TS efficiently induces apoptosis in leukemic cells, which may be a useful therapeutic modality in CML patients.     

Ultracytochemical studies on leukemic cells]

The present survey of ultracytochemical investigations in the cells of the Graffi and Rauscher leukaemic systems is intended to throw a light on the place of replication and on the incorporation of cell specific material into the virus. The successful evidence of incorporating certain enzymes associated to the membrane into the virus envelope could have a significance in so far as this process can be used to explain the appearance of cytotropism in certain kinds of virus to a target cell.     

Clever leukemic stem cells branch out

Individual tumors harbor heterogeneous populations of genetically distinct subclones. Two recent papers in Nature by Notta et al. (2011) and Anderson et al. (2011) reveal genetic heterogeneity in functional leukemic stem cells, which has important implications for how both cancer and normal stem cell populations may adapt to selective pressure.