scholarly journals Antileukemic activity of novel adenosine derivatives

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anastazja Poczta ◽  
Aneta Rogalska ◽  
Małgorzata Łukawska ◽  
Agnieszka Marczak
Keyword(s):  
Cell Cycle ◽  
Intracellular Calcium ◽  
Caspase 3 ◽  
Dna Lesions ◽  
Proteinase K ◽  
Leukemic Cells ◽  
Acute Monocytic Leukemia ◽  
Monocytic Leukemia ◽  
High Cytotoxicity ◽  
Atr Kinase

Abstract The present study investigated the effect of cladribine (CLA) and six of its derivatives containing a formamidine group at position 6 (CLA-FDM, CLA-FPAZ, CLA-FPIR, CLA-FPIP, CLA-FHEX, and CLA-FMOR) on acute promyelocytic, lymphoblastic, and acute monocytic leukemia cells. The role of ATR kinase in deoxycytidine kinase (dCK) activation in response to DNA damage was assessed. The presence of DNA lesions was assessed by measurement phosphorylation of H2AX and by using the alkaline comet assay with proteinase K post-treatment following assessment of the cell cycle. Apoptotic events such as alterations in intracellular calcium concentration, caspase-3/7 activity and increased sub-G1 cell population were measured. CLA derivatives were highly effective against leukemic cells, showing high cytotoxicity, causing DNA fragmentation, and inducing DNA-protein cross-links in leukemic cells. CLA-FMOR showed the highest efficacy. CLA derivatives increased the levels of intracellular calcium ions, caspase-3/7 and the percentage of sub-G1 apoptotic cells and blocked cells in the S phase of the cell cycle to a greater extent than free CLA. The selective ATR inhibitor VE-821 significantly suppressed the increase in dCK activity and decreased basal dCK activity. The present results suggested that ATR kinase controls dCK activity in response to synthetic CLA derivatives.

scholarly journals Studies in acute leukemia. I. Antibody-dependent and spontaneous cellular cytotoxicity by leukemic blasts from patients with acute nonlymphoid leukemia

Blood ◽  
1979 ◽  
Vol 54 (3) ◽  
pp. 573-580
Author(s):  
G Fernandes ◽  
T Garrett ◽  
M Nair ◽  
D Straus ◽  
RA Good ◽  
...  
Keyword(s):  
Fc Receptors ◽  
Surface Antigens ◽  
Leukemic Cells ◽  
Acute Monocytic Leukemia ◽  
Cellular Cytotoxicity ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Adcc Activity ◽  
Monocytic Leukemia ◽  
K562 Cell Line ◽  
Cell Surface Antigens

Leukemic blasts from patients with acute nonlymphoid leukemia were examined for the presence of Ig, receptors for IgGFc, and for their capacity to mediate antibody-dependent cellular cytotoxicity (ADCC) against chicken red blood cells (RBC) coated with IgG and spontaneous cell-mediated cytotoxicity (SCMC) against cells of K562 cell line. Leukemic blasts from acute myeloblastic leukemia (AML) patients lacked both Fc receptors and Ig on their surface, had no SCMC activity and majority, but not all of them, lacked ADCC activity. Leukemic blasts from patients with acute monocytic leukemia (AMOL) had Fc receptors, and 50% had IgG on their surface. IgG was cytophilic and appeared not to be directed against cell-surface antigens. This antibody did not interfere with the ADCC activity of leukemic cells. Leukemic blasts from majority of patients with AMOL mediated ADCC, but had no SCMC activity. An association between ADCC and presence of Fc receptor was observed.

Human Monocytoid Leukemia Cells Are Highly Sensitive to Apoptosis Induced by 2′-Deoxycoformycin and 2′-Deoxyadenosine: Association With dATP-Dependent Activation of Caspase-3

Blood ◽  
1998 ◽  
Vol 92 (9) ◽  
pp. 3368-3375 ◽  
Author(s):  
Nozomi Niitsu ◽  
Yuri Yamaguchi ◽  
Masanori Umeda ◽  
Yoshio Honma
Keyword(s):  
Cell Lines ◽  
Caspase 3 ◽  
Lymphoma Cell ◽  
Leukemia Cells ◽  
Acute Monocytic Leukemia ◽  
U937 Cells ◽  
Monocytic Leukemia ◽  
Low Concentrations ◽  
American Society ◽  
Induced Apoptosis

Abstract The adenosine deaminase (ADA) inhibitor 2′-deoxycoformycin (dCF) significantly inhibits the proliferation of leukemia and lymphoma cell lines. When cells were incubated in the presence of both dCF and 2′-deoxyadenosine (dAd), the concentration of dCF required to induce apoptosis of monocytoid leukemia cells was much lower than that required for myeloid, erythroid, or lymphoma cell lines. Among the cell lines tested, U937 cells were the most sensitive to this treatment. The concentration of dCF that effectively inhibited the proliferation of U937 cells was 1/1,000 of that required for lymphoma cell lines, on a molar basis. However, the uptake of dCF or dAd in U937 cells was comparable with that in other leukemia and lymphoma cell lines. The intracellular accumulation of dATP in U937 cells was only slightly higher than that in other leukemia cells in dCF-treated culture. Treatment with dCF plus dAd induced apoptosis in U937 cells at low concentrations, and this apoptosis was reduced by treatment with caspase inhibitors. Induction of caspase-3 (CPP32) activity accompanied the apoptosis induced by dCF plus dAd. No activation of CPP32 was observed in cytosol prepared from exponentially growing leukemia and lymphoma cells. However, dATP effectively induced CPP32 activation in cytosol from monocytoid cells, but not in that from nonmonocytoid cells, suggesting that dATP-dependent CPP32 activation is at least partly involved in the preferential induction of apoptosis in monocytoid leukemia cells. The combination of dCF and dAd may be useful for the clinical treatment of acute monocytic leukemia. © 1998 by The American Society of Hematology.

scholarly journals Cell marker analysis in acute monocytic leukemias

Blood ◽  
1977 ◽  
Vol 49 (6) ◽  
pp. 895-901
Author(s):  
B Koziner ◽  
S McKenzie ◽  
D Straus ◽  
B Clarkson ◽  
RA Good ◽  
...  
Keyword(s):  
Leukemic Cells ◽  
Acute Monocytic Leukemia ◽  
Cell Marker ◽  
Monocytic Leukemia ◽  
Differentiation Markers ◽  
Marker Analysis ◽  
Multiple Differentiation ◽  
Acetate Esterase ◽  
Alpha Naphthyl Acetate Esterase ◽  
Naphthyl Acetate

Leukemic cells from nine cases of acute monocytic leukemia (AMoL) were characterized by multiple differentiation markers. Cells in most cases were phagocytic, carried an Fc receptor, and stained positively for alpha-naphthyl acetate esterase but negatively for naphthol AS-D chloroacetate esterase. However, subtle differences in marker expression were observed which suggested different degrees of leukemic cellular maturation or activation. Cell marker analysis proved to be a useful adjunct to conventional morphology in confirming the diagnosis and the recognition of the neoplastic cells in AMoL, and may ultimately provide insight into the functional state of these cells.

scholarly journals MICROSCOPIC AND HISTOCHEMICAL STUDIES ON THE AUER BODIES IN LEUKEMIC CELLS

Blood ◽  
1950 ◽  
Vol 5 (9) ◽  
pp. 847-863 ◽  
Author(s):  
G. ADOLPH ACKERMAN
Keyword(s):  
Periodic Acid ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Acute Monocytic Leukemia ◽  
Desoxyribonucleic Acid ◽  
Monocytic Leukemia ◽  
Acid Condition ◽  
Periodic Acid Schiff ◽  
Temperature Changes ◽  
Acid And Alkaline Phosphatase

Abstract (1) Seventeen cases of acute leukemia with Auer bodies have been reported. Studies were carried out on 7 cases of acute monocytic leukemia and 3 cases of subacute myelogenous leukemia. (2) Histochemical studies showed the Auer bodies to be oxidase, peroxidase, and periodic acid-Schiff positive; sudanophilic, slightly metachromatic and to give positive tests for acetal lipids and ribonucleic acid. (3) The Auer bodies were negative for acid and alkaline phosphatase, lipase, glycogen, desoxyribonucleic acid and were non-birefringent. (4) A change in the chemical nature of the Auer body from an acid condition to a more neutral state was noted. This change corresponded with the changes of the normal cytoplasmic granulation of the myelocytes and monocytes during maturation. (5) The effects of cellular movements, trauma, and temperature changes upon the Auer bodies were studied. (6) Several leukemic cells, containing Auer bodies, were studied during the process of mitosis. (7) A theory as to the formation and disintegration of the Auer bodies has been presented.

scholarly journals Cell marker analysis in acute monocytic leukemias

Blood ◽  
1977 ◽  
Vol 49 (6) ◽  
pp. 895-901 ◽  
Author(s):  
B Koziner ◽  
S McKenzie ◽  
D Straus ◽  
B Clarkson ◽  
RA Good ◽  
...  
Keyword(s):  
Leukemic Cells ◽  
Acute Monocytic Leukemia ◽  
Cell Marker ◽  
Monocytic Leukemia ◽  
Differentiation Markers ◽  
Marker Analysis ◽  
Multiple Differentiation ◽  
Acetate Esterase ◽  
Alpha Naphthyl Acetate Esterase ◽  
Naphthyl Acetate

Abstract Leukemic cells from nine cases of acute monocytic leukemia (AMoL) were characterized by multiple differentiation markers. Cells in most cases were phagocytic, carried an Fc receptor, and stained positively for alpha-naphthyl acetate esterase but negatively for naphthol AS-D chloroacetate esterase. However, subtle differences in marker expression were observed which suggested different degrees of leukemic cellular maturation or activation. Cell marker analysis proved to be a useful adjunct to conventional morphology in confirming the diagnosis and the recognition of the neoplastic cells in AMoL, and may ultimately provide insight into the functional state of these cells.

scholarly journals Distinct anti-proliferative effects of herbal melanin on human acute monocytic leukemia THP-1 cells and embryonic kidney HEK293 cells

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Adila El-Obeid ◽  
Hala Alajmi ◽  
Mashael Harbi ◽  
Wesam Bin Yahya ◽  
Hamad Al-Eidi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Biological Effects ◽  
Hek293 Cells ◽  
Phase Cell ◽  
Acute Monocytic Leukemia ◽  
Dependent Manner ◽  
Tlr4 Expression ◽  
Monocytic Leukemia ◽  
Cellular Models

Abstract Background Herbal melanin (HM) is a dark pigment extracted from the seed coat of Nigella sativa L. and known to exert biological effects via toll-like receptor 4 (TLR4). Recently, TLR4 was described as involved in natural programmed cell death (apoptosis). Tumor and embryonic cells are used as in vitro cellular models for drug and anti-cancer agent screening. To date, no cytotoxic studies have been reported of HM in TLR4-positive acute monocytic leukemia THP-1 cells compared to TLR4-negative human embryonic kidney HEK293 cells. Methods We studied the anti-proliferative effects of several HM concentrations on THP-1 and HEK293 cells by evaluating cell viability using the CellTiter-Glo® luminescent assay, assessing the TLR4 expression level, determining the apoptotic status, and analyzing the cell cycle distribution using flow cytometry. Apoptotic pathways were investigated using mitochondrial transition pore opening, caspase activity assays and immunoblot technology. Results Low HM concentrations did not affect THP-1 cell viability, but high HM concentrations (62.5–500 μg/mL) did decrease THP-1 cell viability and induced G0/G1 phase cell cycle arrest. Only at the highest concentration (500 μg/mL), HM slightly increased the TLR4 expression on the THP-1 cell surface, concomitantly upregulated TLR4 whole protein and gene expression, and induced apoptosis in THP-1 cells via activation of the extrinsic and intrinsic pathways. No change of apoptotic status was noticed in TLR4-negative HEK293 cells, although HM decreased HEK293 cell viability and induced cell growth arrest in the G2 phase. Conclusion HM exerts distinct anti-proliferative effects on human acute monocytic leukemia and embryonic kidney cells mainly through cell cycle interference in a TLR4-independent manner and through apoptosis induction in a TLR4-dependent manner, as observed in only the THP-1 cells.

scholarly journals Acute monocytic leukemia diagnosed by flow cytometry includes acute myeloid leukemias with weakly or faintly positive non-specific esterase staining

2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Yuriko Zushi ◽  
Miho Sasaki ◽  
Ayano Mori ◽  
Toshiharu Saitoh ◽  
Takae Goka ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Leukemic Cells ◽  
Acute Monocytic Leukemia ◽  
Monocytic Leukemia ◽  
Weak Positivity ◽  
Myeloid Leukemias ◽  
Acute Myeloid

A diagnosis of acute monocytic leukemia(AML-M5) based on α-naphthyl butyrateesterase (α-NB) staining has some problems,because AML-M5 leukemic cells often showweak or faint positivity on α-NB staining. Inthese situations, some cases of AML-M5tend to be misdiagnosed as AML-M0. Therefore, we evaluated the significance ofweak or faint α-NB staining in AML-M5diagnosed by flow cytometry (FCM). Nineteen AML cases in which leukemic cellswere negative for naphthol AS-D chloroac-etate esterase staining were studied. ForFCM, we defined leukemic cells as having amonocytic nature when more than 10% ofthe leukemic cells were positive for at leastone of the following antigens: CD4, CD11c,CD14, and CD64. The monocytic naturedetermined by FCM was consistent with pos-itive or weak positivity on α-NB staining. Five of 6 cases in which leukemic cellsexhibited faint positivity for α-NB stainingcould be diagnosed as AML-M5 by FCM,while negative α-NB staining was consistentwith a diagnosis of AML-M0. These resultssuggest that AML-M5 should be taken intoconsideration even when leukemic cells arefaintly positive for α-NB staining.

scholarly journals Observations on the Effect of Various Folic Acid Antagonists on Acute Leukemia

Blood ◽  
1951 ◽  
Vol 6 (11) ◽  
pp. 1002-1012 ◽  
Author(s):  
SLOAN J. WILSON
Keyword(s):  
Folic Acid ◽  
Acute Leukemia ◽  
Leukemic Cells ◽  
Acute Monocytic Leukemia ◽  
Acute Lymphatic Leukemia ◽  
Older Individuals ◽  
Monocytic Leukemia ◽  
Toxic Reaction ◽  
Lymphatic Leukemia ◽  
Folic Acid Antagonists

Abstract 1. Seventy patients with acute leukemia were treated with various folic acid antagonists. Sixty-five survived for a sufficient length of time to evaluate the effect of the therapeutic agents. Types of leukemia observed included 38 cases of acute lymphatic leukemia, 23 patients with acute monocytic leukemia and 4 with the acute myelogenous type of leukemia. 2. The best results, both clinically and hematologically, were obtained in acute lymphatic leukemia. Although the most satisfactory results were observed in the youngest age group, excellent remissions were produced in older individuals. Of 65 cases observed, an excellent clinical and hematologic remission was observed in 11 patients, a partial emission in 19 subjects, and no response in 35 individuals. 3. When a response occurred, a rater definite hematologic pattern was noted. An increased platelet count in most instances was the first evidence of regeneration and occurred in about the third or fourth week. The neutrophilic polymorphonuclear leukocytes began to regenerate at about the same time and an increase in their number was followed by a rise in the erythrocyte count. 4. Observations of the bone marrow indicated that although excellent clinical and hematologic remissions might occur, primitive leukemic cells were still present. In some instances megaloblasts were observed in addition to a peripheral macrocytosis and anisocytosis of erythrocytes. 5. Toxic manifestations were common. These included glossitis, ulceration of the oral cavity, nausea, vomiting, diarrhea and alopecia. In one instance there was ulceration of the entire gastro-intestinal tract, including the esophagus and colon. Hematologic toxic reactions included thrombocytopenia, leukopenia and anemia. Aplasia of marrow tissue was observed in 1 instance. In many instances the margin of safety between a toxic reaction and death was indeed small. 6. It should be emphasized that in no instance has a cure of leukemia resulted from treatment with a folic acid antagonist although prolonged remissions have occurred.

scholarly journals Functional and morphologic characteristics of the leukemic cells of a patient with acute monocytic leukemia: correlation with clinical features

Blood ◽  
1975 ◽  
Vol 46 (1) ◽  
pp. 17-26 ◽  
Author(s):  
CA Schiffer ◽  
FT Sanel ◽  
BK Stechmiller ◽  
PH Wiernik
Keyword(s):  
Clinical Course ◽  
Light And Electron Microscopy ◽  
Leukemic Cells ◽  
Acute Monocytic Leukemia ◽  
Monocytic Leukemia ◽  
Monocytic Cells ◽  
Morphologic Characteristics ◽  
Cytoplasmic Maturation

Abstract The clinical course of a patient with acute monocytic leukemia and prominent infiltration of the skin and testes is described. In vitro studies demonstrated that the circulating monocyte precursors were capable of adherence to nylon fibers, and phagocytosis of bacteria and latex particles. In vivo, migration of leukemic cells to skin windows was observed. Extreme nuclear folding, marked surface activity, and morphologic features suggesting nuclear and cytoplasmic maturation were seen by light and electron microscopy. The presence of morphologically and functionally more differentiated monocytic cells may account for the marked tiuuse invasion in this patient and, possibly, in other patients with monocytic leukemia.

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