Growth Inhibition and Induction of Differentiation of Human K562 Leukemic Cells by 3′ -Deoxy-3′-Fluorothymidine and Cytosine Arabinoside

1995 ◽  
pp. 141-147
Author(s):  
Peter Langen ◽  
Klaus Eckert ◽  
Tania Fuhrmann-Selter ◽  
Manfred Schütt ◽  
H. Rainer Maurer
Keyword(s):  
Growth Inhibition ◽  
Cytosine Arabinoside ◽  
Leukemic Cells ◽  
Induction Of Differentiation

A simplified assay for measurement of cytosine arabinoside incorporation into DNA in Ara-C-sensitive and-resistant leukemic cells

1990 ◽  
Vol 27 (2) ◽  
pp. 151-156 ◽  
Author(s):  
Louisa P. Colly ◽  
Dick J. Richel ◽  
Willy Arentsen-Honders ◽  
Ingrid W. J. Starrenburg ◽  
Peter M. Edelbroek ◽  
...  
Keyword(s):  
Cytosine Arabinoside ◽  
Leukemic Cells

Induction of differentiation of cultured mouse myeloid leukemic cells by arginase

1979 ◽  
Vol 89 (3) ◽  
pp. 879-884 ◽  
Author(s):  
Junko Okabe ◽  
Moriaki Hayashi ◽  
Yoshio Honma ◽  
Motoo Hozumi
Keyword(s):  
Leukemic Cells ◽  
Induction Of Differentiation

scholarly journals Induction of differentiation of WEHI-3B D+ leukemic cells transfected with differentiation-stimulating factor/leukemia inhibitory factor receptor cDNA

Blood ◽  
1995 ◽  
Vol 85 (1) ◽  
pp. 217-221 ◽  
Author(s):  
M Tomida
Keyword(s):  
Leukemia Inhibitory Factor ◽  
Oncostatin M ◽  
Inhibitory Factor ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Leukemia Inhibitory Factor Receptor ◽  
Transfected Cells ◽  
Receptor Cdna ◽  
Induction Of Differentiation ◽  
Stimulating Factor

Differentiation-stimulating factor (D-factor)/leukemia inhibitory factor can induce the differentiation of mouse myeloid leukemia M1 cells and also stimulate proliferation of the interleukin-3 (IL-3)- dependent cell line, DA-1a. To determine whether D-factor can induce the differentiation of leukemia cells other than M1 cells, WEHI-3B D+ mouse myelomonocytic leukemia cells were transfected with a plasmid containing mouse D-factor receptor cDNA. Expression of D-factor receptor in transfected cells was determined by binding of [125]D- factor and analyzed by Scatchard's method. The transfected cells had high-affinity D-factor receptors with a dissociation constant of 100 to 200 pmol/L and binding sites per cell varied from 67 to 1,500 among several clones. The cells expressing a high level of D-factor receptor were induced to differentiate by D-factor; about 60% of the cells exhibited the ability to reduce nitroblue tetrazolium and expression of the differentiation antigen Mac-1 (CD11b) on the cell surface increased. The effect of cytokines, which induce the differentiation of M1 cells, on the transfected WEHI-3B cells was examined. The sensitivity to oncostatin M was identical to that against D-factor in the cells of each clone. Expression of D-factor receptor in WEHI-3B cells promoted sensitivity to IL-6 and granulocyte colony-stimulating factor (G-CSF). Induction of differentiation of the cells accompanied the suppression of proliferation. Treatment of the cells with D-factor for longer than 5 days resulted in 50% inhibition of growth. These results indicate that the stimulating effect of D-factor on the differentiation of malignant myeloid cells is not unique to M1 cells.

scholarly journals Effect of M20 interleukin-1 inhibitor on normal and leukemic human myeloid progenitors

Blood ◽  
1992 ◽  
Vol 79 (5) ◽  
pp. 1172-1177 ◽  
Author(s):  
T Peled ◽  
M Rigel ◽  
D Peritt ◽  
E Fibach ◽  
AJ Treves ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Interleukin 1 ◽  
Hematopoietic Cells ◽  
Myeloid Cell ◽  
Leukemic Cells ◽  
True Negative ◽  
In Vitro Proliferation ◽  
Gm Csf ◽  
Liquid Systems

Abstract This study aimed to assess the effect of the M20 interleukin-1 (IL-1) inhibitor on normal and leukemic hematopoietic cells. The M20-derived IL-1 inhibitor was found to inhibit the growth of various hematopoietic cells. The in vitro proliferation of myeloid cell lines in serum- containing medium or proliferation of these cells induced by IL-1 in serum-free medium (measured by 3H-TdR) were inhibited by the M20 IL-1 inhibitor. In addition, growth of normal progenitors and fresh leukemic cells stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) (as measured by colony and liquid systems) was also inhibited by this factor. After the removal of the IL-1 inhibitor at the peak of growth inhibition, leukemic and normal progenitor cells retain their ability to grow and develop into GM-CSF colonies. These results show that the growth inhibition phenomena were reversible and did not result from a cytotoxic effect. Our data suggest that the M20-derived IL-1 inhibitor might function as a true negative growth regulator of normal and leukemic hematopoietic cells.

scholarly journals Inhibition of differentiation and affinity purification with a monoclonal antibody to a myeloid cell differentiation-inducing protein

Blood ◽  
1988 ◽  
Vol 72 (5) ◽  
pp. 1543-1549 ◽  
Author(s):  
Y Shabo ◽  
L Sachs
Keyword(s):  
Monoclonal Antibody ◽  
Affinity Purification ◽  
Myeloid Cell ◽  
Leukemic Cells ◽  
Endogenous Production ◽  
Mouse Macrophages ◽  
Induction Of Differentiation ◽  
Inhibition Of Differentiation ◽  
Necrosis Factor

Abstract The normal myeloid hematopoietic regulatory proteins include four growth-inducing proteins called colony-stimulating factors (CSF), including interleukin-3 (IL-3), or macrophage and granulocyte inducers, type 1 (MGI-1), and another type of protein (MGI-2) with no myeloid cell growth-inducing activity that induces differentiation of normal myeloid precursor cells and certain clones of myeloid leukemic cells. An IgG2a monoclonal antibody was prepared and it neutralized two forms of MGI-2 (MGI-2A and MGI-2B) produced by mouse Krebs ascites tumor cells. The monoclonal antibody was used for affinity purification of MGI-2. This antibody also neutralized MGI-2 produced by normal mouse macrophages, normal myeloblasts incubated with IL-3, and MGI-2 produced by the lungs and found in the serum of mice injected with lipopolysaccharide (LPS). The anti-MGI-2 antibody did not inhibit the activity of any one of the four myeloid growth-inducing proteins (CSF or IL-3 = MGI-1), IL-1, tumor necrosis factor, or lymphotoxin. This antibody also inhibited induction of differentiation of myeloid leukemic cells by LPS, which is mediated by the endogenous production of MGI-2, but did not inhibit induction of differentiation in these leukemic cells by dexamethasone or cytosine arabinoside, which is not mediated by MGI-2. Anti-MGI-2 antibody thus inhibited differentiation when MGI-2 was added externally to cells or when it was mediated by endogenously produced MGI-2.

scholarly journals Anti-CD33 monoclonal antibody and etoposide/cytosine arabinoside combinations for the ex vivo purification of bone marrow in acute nonlymphocytic leukemia

Blood ◽  
1991 ◽  
Vol 77 (2) ◽  
pp. 355-362 ◽  
Author(s):  
PJ Stiff ◽  
WC Schulz ◽  
M Bishop ◽  
L Marks
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Cytosine Arabinoside ◽  
Ex Vivo ◽  
Leukemic Cells ◽  
Acute Nonlymphocytic Leukemia ◽  
Drug Concentrations ◽  
Pharmacologic Agents

Abstract Pharmacologic and immunologic methods of ex-vivo bone marrow (BM) purging for acute nonlymphocytic leukemia (ANLL) were combined to augment the effect of either method alone. Etoposide (VP16; 20 to 30 micrograms/mL) with or without cytosine arabinoside (Ara C; 10 mg/mL) was used in tandem with the anti-CD33 monoclonal antibody (MoAb), MY9, chosen because CD33 is found on the stem cell pool in the majority of patients with ANLL. The agents were tested singly or sequentially, with a 1-hour incubation of the drugs preceding complement-mediated lysis using MY9. VP16 combined with Ara C killed up to 3.9 +/- 0.3 and 5.11 +/- 0.4 logs of the human ANLL cell lines HL60 and K562 at drug concentrations that killed only 1.2 +/- 0.1 logs of normal committed granulocyte/macrophage stem cells (CFU-GM). Adding a single exposure of the MY9 and complement (C′) to the drug-treated cells, greater than 5.4 logs of HL60 were killed. Similar to other pharmacologic agents, no differential kill for clonagenic leukemic cells (colony-forming unit- leukemia; CFU-L) from patients with ANLL was seen for drug only treated blasts versus normal CFU-granulocyte-macrophage (CFU-GM), with less than 1 log CFU-L kill at drug concentrations that spared 1 log of CFU- GM. Similarly, only 1.1 +/- 0.3 logs of ANLL CFU-L were eliminated using MY9 and C′. However, with the sequential VP16/Ara C----MY9 + C′ treatment, synergy was demonstrated and 2.6 +/- 0.3 logs of CFU-L were eliminated. Because CD33 is also found on the normal CFU-GM pool, two- stage long-term BM cultures were performed to determine pluripotent stem cell elimination by the drug/MoAb purging combination. No difference of CFU-GM or BFU-E production at 4 to 6 weeks of culture for VP16/Ara C, MY9 + C′, or VP16/AraC----My9 + C′ treated cells was seen compared with untreated controls indicating sparing of early progenitor cells. Sequential ex vivo treatment of human ANLL CFU-L with VP16/Ara C followed by complement-mediated lysis using MY9 synergistically kills CFU-L while sparing early normal hematopoietic progenitor cells, and thus may be a more effective way to purge BM than either alone.

Protection of leukemic cells by deoxycytidine: in vitro measures of protection against cytosine arabinoside

1998 ◽  
Vol 22 (5) ◽  
pp. 421-427
Author(s):  
Justin D Cohen ◽  
David J Strock ◽  
Elizabeth A LaGuardia ◽  
Zhi Mao ◽  
Joanne E Teik
Keyword(s):  
Cytosine Arabinoside ◽  
Leukemic Cells

scholarly journals Regulation of acid phosphatase activity in human promyelocytic leukemic cells induced to differentiate in culture.

1979 ◽  
Vol 83 (2) ◽  
pp. 300-307 ◽  
Author(s):  
A Vorbrodt ◽  
P Meo ◽  
G Rovera
Keyword(s):  
Endoplasmic Reticulum ◽  
Acid Phosphatase ◽  
Smooth Endoplasmic Reticulum ◽  
Leukemic Cell ◽  
Time Sequence ◽  
Leukemic Cells ◽  
Leukemic Cell Line ◽  
Faint Band ◽  
Induction Of Differentiation ◽  
Sequence Study

Induction of differentiation of a human promyelocytic leukemic cell line (HL60) in culture is accompanied by changes in acid phosphatase (Acpase) activity. The increase in activity is less than twofold when the leukemic cells are stimulated by dimethylsulfoxide (DMSO) to differentiate into metamyelocytes and granulocytes but is eightfold when the cells are stimulated by the tumor-promoting agent 12-0-tetradecanoylphorbol 13-acetate (TPA) to differentiate into macrophage-like cells. Five different isozymes of Acpase were separated by acrylamide gel electrophoresis. Isozyme 1, the most anodal isozyme, was found to be present in undifferentiated, DMSO-treated and TPA-treated cells; isozyme 2 was a very faint band observed both in DMSO- and TPA-treated cells, the isoenzymes 3a and 3b were present only in TPA-induced cells; and isozyme 4, the most cathodal isozyme, was present both in TPA- and DMSO-induced cells. A time sequence study on the appearance of the various forms after TPA treatment indicated that the expression of the isozymes is regulated in an uncoordinated fashion. Acpase activity has been shown by ultrastructural cytochemistry to be localized in the entire rough endoplasmic reticulum (RER) and in areas of the smooth endoplasmic reticulum (SER) located near the Golgi complex in differentiating cells but to be extremely weak, if at all detectable, in undifferentiated promyelocytes.

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