Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Normal granulocyte-monocyte progenitor cells have an absolute requirement for colony-stimulating factor (CSF) for proliferation and differentiation in vitro. In contrast, cells derived from acute myeloblastic leukemia patients are often defective in their response to CSF, but can be induced to undergo terminal differentiation by exposure to 12-o-tetradecanoyl phorbol-13-acetate (TPA) by a process that does not require cell proliferation. To investigate the relationship between TPA-induced leukemic cell differentiation and CSF-induced myeloid cell differentiation we investigated the effects of TPA on myeloblasts highly enriched from normal bone marrow and stable-phase chronic myeloid leukemia peripheral blood. TPA (10(-6)-10(-9) M) induced the rapid appearance of macrophage characteristics in the majority of myeloblasts in the absence of proliferation. The mechanisms of TPA- and CSF-induced myeloblast differentiation were compared by examining the requirement for DNA synthesis. Exposure of myeloblasts to CSF induced increased triatiated thymidine (3H-TdR) incorporation within a few hours, while TPA did not induce 3H-TdR incorporation by itself and was inhibitory to CSF-induced 3H-TdR uptake. This requirement for DNA synthesis was further investigated by reversibly inhibiting DNA synthesis by depleting intracellular polyamines with difluoromethylorinithine (DFMO). DFMO inhibited both CSF-induced proliferation and differentiation of myeloblasts, but had no effect on TPA-induced differentiation. These results demonstrate that the process of differentiation of myeloblasts induced by TPA is distinct from CSF-induced differentiation.
 ...
PMID:TPA induces differentiation of purified human myeloblasts in the absence of proliferation. 393 87

The alterations of stimulus-induced membrane potential changes, superoxide (O2-)-producing capacity and phagocytic activity during differentiation of human granulocytes were investigated in the human leukemia cell lines HL-60 and KG-1 differentiating in vitro and in human leukemic granulocytes obtained from chronic myelogenous leukemia patients. HL-60 cells incubated with dimethyl sulfoxide or with retinoic acid showed progressively increasing O2- production as well as membrane potential changes (depolarization) on contact with phorbol myristate acetate or the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine, with a concomitant increase in the proportion of mature cells of the granulocytic type. Phagocytosis of latex particles, yeast, and oil droplets appeared 24 h after incubation with dimethyl sulfoxide and anteceded the increment of O2- production and membrane potential changes, both of which appeared concomitantly 3 d after incubation with dimethyl sulfoxide. Similar findings were observed when immature and mature granulocytes obtained from chronic myelogenous leukemia patients were stimulated by phorbol ester, the chemotactic peptide, or calcium ionophore A23187, and the amount of O2- production was parallel to the magnitude of membrane potential changes. HL-60 and KG-1 cells incubated for 1-6 d with phorbol myristate acetate showed neither O2- production nor membrane potential changes on contact with phorbol ester, chemotactic peptide, or A23187, although such cells resembled macrophages morphologically, and their phagocytic activity was significantly increased. O2- production and membrane potential changes in normal granulocytes induced by phorbol ester, chemotactic peptide and A23187 were inhibited by 2-deoxyglucose. These findings indicate that the O2--producing system and the system provoking membrane potential changes may develop concomitantly as human granulocytes mature and differentiate, and that the development of these systems and of phagocytic activity may be independently regulated.
 ...
PMID:Functional maturation of membrane potential changes and superoxide-producing capacity during differentiation of human granulocytes. 620 May 1

Two different Fc receptors for IgG (Fc gamma R) have been identified on human leukocytes: a high avidity receptor (Fc gamma Rhi) present on monocytes but not on neutrophils, and a low avidity receptor (Fc gamma Rlo) present on neutrophils but not on monocytes. Fc gamma Rlo can be inhibited and the receptor precipitated by monoclonal antibody 3G8. We have used this monoclonal antibody to study the course of Fc gamma Rlo appearance on bone marrow cells, leukocytes of patients with chronic myelogenous leukemia (CML), and HL-60 and U937 cells induced to differentiate with agents such as dimethyl sulfoxide (DMSO), retinoic acid, phorbol myristate acetate, and lymphokine. We report that Fc gamma Rlo is a late differentiation antigen, first expressed at the metamyelocyte stage. Since precursors to metamyelocytes bear Fc gamma R, and the promyelocyte line HL-60 bears Fc gamma Rhi, there must be a progressive loss of Fc gamma Rhi during myeloid differentiation and the reciprocal expression of Fc gamma Rlo. Results of immunoprecipitation and polyacrylamide gel analysis of the proteins are consistent with these results. We have also studied the receptor for the C3bi complement component (CR3), which is blocked and immunoprecipitated by monoclonal antibody OKM10. During DMSO-driven differentiation of HL-60 cells, we find that CR3 is induced on all cells, whereas Fc gamma Rlo is induced on only 24% of cells, suggesting that CR3 appears earlier during differentiation than Fc gamma Rlo does.
 ...
PMID:Ontogeny of Fc receptors and complement receptor (CR3) during human myeloid differentiation. 623 Mar 73

Freshly isolated human leukemia cells have been shown in the past to display varying in vitro responses to phorbol diesters, depending on their cell type. Specific receptors for the phorbol diesters have been demonstrated on numerous different cells. This study was designed to characterize the receptors for phorbol diesters on leukemia cells freshly isolated from patients with different kinds of leukemia and to determine if differences in binding characteristics for tritium-labeled phorbol 12,13-dibutyrate (3H-PDBu) accounted for the different cellular responses elicited in vitro by phorbol diesters. Cells from 26 patients with different kinds of leukemia were studied. PDBu or phorbol 12-myristate 13-acetate (PMA) caused cells from patients with acute myeloblastic leukemia (AML), acute promyelocytic (APML), acute myelomonocytic (AMML), acute monocytic (AMoL), acute erythroleukemia (AEL), chronic myelocytic leukemia (CML) in blast crisis (myeloid), acute undifferentiated leukemia (AUL), and hairy cell leukemia (HCL) (n = 15) to adhere to plastic and spread. However, they caused no adherence or spreading and only slight aggregation of cells from patients with acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), or CML-blast crisis (lymphoid) (n = 11). All leukemia cells studied, irrespective of cellular type, displayed specific receptors for 3H-PDBu. The time courses for binding by all leukemia types were similar, with peak binding at 5-10 min at 37 degrees C and 120 min at 4 degrees C. The binding affinities were similar for patients with ALL (96 +/- 32 nM, n = 4), CLL (126 +/- 32 nM, n = 6), and acute nonlymphoid leukemia (73 +/- 14 nM, n = 11). Likewise, the numbers of specific binding sites/cell were comparable for the patients with ALL (6.2 +/- 1.3 X 10(5) sites/cell, n = 4), CLL (5.0 +/- 2.0 X 10(5) sites/cell, n = 6), and acute nonlymphoid leukemia (4.4 +/- 1.9 X 10(5) sites/cell, n = 11). Thus, the differing responses to phorbol diesters of various types of freshly isolated leukemia cells appear to be due to differences other than initial ligand-receptor binding.
 ...
PMID:Specific receptors for phorbol diesters on freshly isolated human myeloid and lymphoid leukemia cells: comparable binding characteristics despite different cellular responses. 631 66

Various chemical inducers have effects on the induction of terminal differentiation of human myelogenous leukemia cell lines. We studied morphological and functional changes of human leukemia cells freshly obtained from patients using 12-0-tetradecanoyl phorbol-13-acetate (TPA), retinoic acid (RA) or dimethyl sulphoxide (DMSO). The myeloid leukemia cells cultured with TPA became adherent to plastic culture dishes, and then developed macrophage-like morphology with long filamentous pseudopods within 48 h incubation. They showed marked enhancement of the ability to phagocytose latex particles. But these acquired properties did not always parallel each other, suggesting that the mechanism of functional maturation of leukemic cells induced by chemical agents was not identical with that of morphological changes. On the other hand, the lymphoid leukemia cells did not show morphological and functional changes when cultured with the above inducers. It is suggested that exposure of leukemic cells to TPA for relatively short times (12-24 h) may be useful for determining whether they are of myeloid or lymphoid origin. These characteristic changes were also observed in leukemic cells from the myeloid or lymphoid crisis of chronic myelogenous leukemia.
 ...
PMID:Differentiation of human leukemia cells and its usefulness for clinical diagnosis. 657 51

Normal human monocytes and macrophages, as well as in vitro human leukaemic promyelocytic cell line (HL-60) transformed into macrophage-like cells by 12-0-tetradecanoylphorbol-13-acetate (TPA) generate potent procoagulant activity (PCA) similar to tissue thromboplastin. In the present study, only mild PCA was detected in primary cultures of cells from the peripheral blood of patients with acute lymphatic leukaemia (ALL), acute myeloid leukaemia (AML) and chronic myeloid leukaemia (CML). After exposure to TPA, AML and CML cells assumed characteristics specific to monocytes and macrophages. Differentiation was associated with the generation of PCA. PCA was not found in ALL cells exposed to TPA. The PCA of TPA-induced macrophages derived from AML and CML cells resembled tissue thromboplastin and normal monocyte and macrophage PCA in several aspects: (a) accelerated clotting via the extrinsic coagulation pathway, (b) inhibition by concanavalin A and protection against lectin inhibition by methyl-alpha-D-mannopyranoside, (c) localization in the cell membrane. The capacity for PCA generation is additional evidence for the similarity between TPA-induced macrophages derived from AML and CML cells and normal human monocytes and macrophages.
 ...
PMID:Generation of procoagulant activity (PCA) by macrophage-like cells derived from acute and chronic myeloid leukaemia cells in response to phorbol esters. 657 80

Human hairy cell leukemia (HCL) cells in culture showed a marked increase in both [1-14C]acetate and [14C]choline incorporation into phosphatidylcholine (PC) when treated with a 10 nM concentration of 12-O-tetradecanoylphorbol 13-acetate (TPA) for 3 h. Dramatic morphological changes occurred and synthesis of most phospholipids was stimulated. However, the most dramatic increase was seen in the [14C]acetate labeling of both long- and short-chain fatty acid-containing sphingomyelins (from 200-425% of control levels), sphingomyelin being especially enriched in HCL cells. Negligible incorporation of [14C]choline into sphingomyelin was observed and phospholipase inhibitor (U10029A) studies indicated that PC was the major source of sphingomyelin choline. These changes were most clearly seen by autoradiography of two-dimensional thin-layer chromatography plates. Chronic myelogenous leukemia (CML) blasts, which did not respond morphologically to TPA, showed no increased phospholipid synthesis under the same conditions and increases in sphingomyelin synthesis were modest. Other non-TPA-responding leukemic cells were similarly refractive. However, one out of four acute monomyelocytic leukemic (AMMoL) cells studied responded morphologically in a manner identical to HCL cells and exhibited the same dramatic increase in sphingomyelin synthesis. Data are presented which suggest that TPA may also stimulate PC phospholipase C activity in addition to activating the calcium-dependent protein kinase by mimicking diacylglycerol.
 ...
PMID:Phorbol ester tumor promoters specifically stimulate choline phospholipid metabolism in human leukemic cells. 659 31

The effects of 12-O-tetradecanoyl phorbol-13-acetate (TPA) on CFU-C were investigated. Exposure of normal bone marrow cells or peripheral blood cells from chronic myeloid leukemia patients to TPA stimulated cluster formation in agar in the absence of added colony-stimulating factors (CSF). In the presence of CSF, TPA inhibited colony and cluster formation. After enrichment of CFU-C approx. 50-fold by an immune rosette technique, TPA-induced stimulation of cluster formation in the absence of CSF was markedly diminished, while the inhibitory effect in the presence of CSF was unchanged. These results suggest that TPA may have complex effects on CFU-C; indirectly promoting colony formation by inducing other cells to secrete CSF, and directly inhibiting CFU-C proliferation.
 ...
PMID:Effect of phorbol ester on differentiation of human myeloid colony forming cells (CFU-C). 660 Dec 21

We report a case of chronic myelogenous leukemia (CML) associated with pronounced peripheral lymphadenopathy, with the cells having the philadelphia (Phl) chromosome and T-cell features. A 23-year-old man who was diagnosed as having CML and treated with busulfan was admitted to our hospital because of increasing hepatosplenomegaly and pronounced lymphadenopathy. An axillary lymph node biopsy disclosed that the malignant cells formed rosettes with neuraminidase-treated sheep red blood cells (En) (95.0%) and were positive for Leu 1 (91.8%). Of the cytochemical reactions, peroxidase was negative and periodic acid-Shiff, acid alpha-naphthyl acetate esterase and beta-glucuronidase were all positive. The karyotype of the bone marrow cells was 46 XY Phl positive (22q-), and that of the lymph node cells was 51 XY Phl positive +8, +9, +18, +19, +21, 22q-. He was treated with various anti-leukemic agents and irradiation. Despite such treatments, he died of pneumonia. This is a report of a CML patients with blast crisis and tumor formation characterized by T-cell features.
 ...
PMID:Blast crisis of chronic myelogenous leukemia with tumor formation characterized by T-cell features--a case report. 660 8

The level of sialyltransferase activity in leukaemic blasts from acute lymphoblastic leukaemia (ALL) cases was significantly lower (3.29 +/- 2.09 pmoles/5 X 10(7) cells or 1.77 +/- 1.16 pmoles/mg protein) than those (18.80 +/- 4.91 pmoles/5 X 10(7) cells or 7.72 +/- 1.75 pmoles/mg protein) of mature lymphocytes from normal volunteers (T less than 0.001). An inverse relationship between the level of sialyltransferase activity and the level of terminal transferase (TdT)activity was seen in blasts from eight TdT-positive ALL cases. No significant difference was observed in the level of sialyltransferase activity between ALL and cells of chronic myelogenous leukemia (CML) in blast crisis. Short Term culture of ALL blast cells with 12-0-tetradecanoylphorbol-13-acetate (TPA) at the concentration of 10-(6)M to 10-(9)M caused a marked increase in sialyltransferase activity. In one of these three ALL cases the population of TdT-positive cells and the TdT activity of the blasts decreased significantly after culture with TPA. These results suggest that biochemical differentiation of leukaemic lymphoblasts has been induced by the addition of TPA, although morphological changes were not observed. Sialyltransferase activity may be a useful indicator for the analysis of differentiation of lymphocytes.
 ...
PMID:Sialyltransferase activity as a marker for the differentiation of lymphocytes. Increase in sialyltransferase activity of blasts from acute lymphoblastic leukaemia cases by 12-o-tetradecanoylphorbol-13-acetate (TPA). 695 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>