Acute monocytic leukemia is a distinct subtype of acute myeloid leukemia (AML) with characteristic biology and clinical features. This study was designed to compare the immunophenotypical features and clinical manifestations of the patients with AML-M(5a) to that of patients with AML-M(5b), and to identify differences between M(5a) and M(5b) and to explore their relations. A total of 58 cases of de novo adult patients with AML M(5) were investigated. Immunofluorescence analysis by flow cytometry was performed to determine the immunophenotype of the leukemic cells in all cases. Meanwhile, clinical data of these cases were studied retrospectively. The results showed that the immunophenotypes of monocytic leukemic cells in patients with AML M(5) were heterogeneous, and CD68 and CD11b were expressed higher in patients with AML M(5a), compared with that in patients with AML M(5b) (P < 0.01). The significant differences in sex, extramedullary infiltration, WBC counts of peripheral blood, complete remission rate and disease-free survival (DFS > 300 days) between the patients with AML M(5a) and M(5b) did not exist (P > 0.05). It is concluded that the special individual immunophenotype features can be detected in patients with either of AML M(5a) or M(5b), and that expressions of CD68 and CD11b were much higher in M(5a). It seems that the complete remission rate and disease-free survival of patients with M(5a) and M(5b) are not different from that of currently available therapy.
Adolescent ; Adult ; Antigens, CD ; analysis ; Antigens, Differentiation, Myelomonocytic ; analysis ; CD11b Antigen ; analysis ; Female ; Fluorescent Antibody Technique ; Humans ; Immunophenotyping ; Leukemia, Monocytic, Acute ; classification ; immunology ; Male ; Middle Aged ; Prognosis

BACKGROUND/AIMS: For unknown reasons, caspase-1 -/- mice, protected against cisplatin-induced acute renal failure (ARF), are deficient in interleukin (IL)-1alpha. We thus asked whether IL-1alpha deficiency underlies the mechanism of protection against cisplatin-induced ARF in these mice. METHODS: Cisplatin (30 mg/kg) was injected intraperitoneally into wild-type C57BL/6 mice to produce a cisplatin-induced model of ARF. IL-1alpha was measured in control vehicle- and cisplatin-treated wild-type animals. We also examined whether IL-1alpha -/- mice were similarly protected against cisplatin-induced ARF. Additionally, infiltration of CD11b- and CD49b-positive cells, as markers of macrophages, natural killer, and natural killer T cells (pan-NK cells), was investigated in wild-type and IL-1alpha -/- mice. RESULTS: Compared with vehicle-treated mice, renal IL-1alpha increased in cisplatin-treated wild-type mice beginning on day 1. IL-1alpha -/- mice were shown to be protected against cisplatin-induced ARF. No significant difference in the infiltration of neutrophils or CD11b- and CD49b-positive cells were observed between wild-type and IL-1alpha -/- mice. CONCLUSIONS: Mice deficient in IL-1alpha are protected against cisplatin-induced ARF. The lack of IL-1alpha may explain, at least in part, the protection against cisplatin-induced ARF observed in caspase-1 -/- mice. Investigation of the protective mechanism (s) in IL-1alpha -/- mice in cisplatin-induced ARF merits further study.
Acute Kidney Injury/chemically induced/*immunology/pathology/physiopathology/prevention & control ; Animals ; Antigens, CD11b/analysis ; Apoptosis ; Biological Markers/blood ; Blood Urea Nitrogen ; *Cisplatin ; Creatinine/blood ; Disease Models, Animal ; Fluorescent Antibody Technique ; Integrin alpha2/analysis ; Interleukin-1alpha/deficiency/genetics/*metabolism ; Kidney/*immunology/pathology/physiopathology ; Killer Cells, Natural/immunology ; Macrophages/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Natural Killer T-Cells/immunology ; Necrosis ; Neutrophil Infiltration ; Time Factors

The possibility that P2X7 receptor (P2X7R) expression in microglia would mediate neuronal damage via reactive oxygen species (ROS) production was examined in the APPswe/PS1dE9 mouse model of Alzheimer's disease (AD). P2X7R was predominantly expressed in CD11b-immunopositive microglia from 3 months of age before Abeta plaque formation. In addition, gp91phox, a catalytic subunit of NADPH oxidase, and ethidium fluorescence were detected in P2X7R-positive microglial cells of animals at 6 months of age, indicating that P2X7R-positive microglia could produce ROS. Postsynaptic density 95-positive dendrites showed significant damage in regions positive for P2X7R in the cerebral cortex of 6 month-old mice. Taken together, up-regulation of P2X7R activation and ROS production in microglia are parallel with Abeta increase and correlate with synaptotoxicity in AD.
Aging ; *Alzheimer Disease/genetics/metabolism/pathology ; Amyloid beta-Peptides ; Animals ; Antigens, CD11b/immunology ; Blotting, Western ; Cerebral Cortex/metabolism/*pathology ; Disease Models, Animal ; Gene Expression ; Mice ; Mice, Transgenic ; Microglia/*metabolism/pathology ; Neurons/metabolism/*pathology ; Plaque, Amyloid ; Reactive Oxygen Species/*metabolism ; Receptors, Immunologic/analysis ; Receptors, Purinergic P2X7/*genetics/metabolism

OBJECTIVETo investigate whether phenylbutyrate (PB) combined with 5-aza-2'-deoxycytidine (5-Aza-CdR)could inhibit transcription repression and induce t(8;21) acute myelogenous leukemia (AML) Kasumi-1 cells to differentiate and undergo apoptosis.

METHODSKasumi-1 cells were treated with PB and 5-Aza-CdR at different concentrations in suspension culture. Cellular proliferation was determined by the MTT assay, expression of myeloid-specific differentiation antigen and cell cycles were analyzed by flow cytometry. Cell apoptosis were assessed using AnnexinV/PI staining and flow cytometry.

RESULTSTreatment of Kasumi-1 cells with PB caused a dose-dependent inhibition of proliferation, with an IC(50) of 2.3 mmol/L. When combined with 5-Aza-CdR, PB resulted in a greater growth inhibition with an IC(50) of 1.95 mmol/L. Treatment of Kasumi-1 cells with PB resulted in cell cycle arrest at G(0)/G(1), while combined treatment with PB and 5-Aza-CdR led to cell cycle arrest at G(2)/M. Expression of myeloid cell differentiation antigens CD11b and CD13 induced by PB was enhanced when Kasumi-1 cells were pretreated with low dose of 5-Aza-CdR. High, but not low, concentrations of 5-Aza-CdR could enhance early apoptosis of Kasumi-1 cells induced by PB.

CONCLUSIONPhenylbuty rate, when combined with 5-Aza-CdR, inhibits AML cell in vitro proliferation and increases apoptosis in a synergistic fashion.

Acute Disease ; Apoptosis ; drug effects ; Azacitidine ; administration & dosage ; analogs & derivatives ; pharmacology ; CD11b Antigen ; metabolism ; CD13 Antigens ; metabolism ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Drug Synergism ; Humans ; Leukemia, Myeloid ; immunology ; pathology ; Phenylbutyrates ; pharmacology