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.

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

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.

scholarly journals B7-H3 Silencing By RNAi Inhibits Tumor Progression and Enhances Chemosensitivity in U937 Cells

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4813-4813
Author(s):  
Wei Zhang ◽  
Jing Wang ◽  
Yanfang Wang ◽  
Fei Dong ◽  
Mingxia Zhu ◽  
...  
Keyword(s):  
Cell Lines ◽  
U937 Cell ◽  
Hematologic Malignancy ◽  
Acute Monocytic Leukemia ◽  
U937 Cells ◽  
Monocytic Leukemia ◽  
Ki 67 ◽  
Chemotherapy Drugs

Abstract Background : Aberrant expression of the immunoregulatory protein B7-H3 in B7 family has been associated with more advanced disease and poor prognosis in a wide range of cancer. However, the role of B7-H3 in acute monocytic leukemia U937 cells has not been thoroughly investigated. In this study, we examined the gene expression and subcellular localization of B7-H3 in human peripheral blood cells and hematologic malignancy cell lines. Then, we determined the effects of down-regulating B7-H3 expression on U937 cells, which has the highest B7-H3 protein expression in the detected cell lines. Methods : B7-H3 expression in 12 healthy volunteer peripheral blood cell samples and 13 human hematologic malignancy cell lines was determined by RT-PCR, western blot and flow cytometry. B7-H3 knockdown in the U937 cell line was performed using shRNA lentivirus transduction. The effects on cell proliferation, cycle, migration and invasion were investigated by CCK-8 assay, methyl cellulose colony forming assay, PI staining, and transwell assays in vitro. U937 xenograft models were used to assess the effects of B7-H3 on tumorigenicity and Ki-67 and PCNA was detected through immunohistochemical. Changes in cell growth inhibition and apoptosis, when combined with chemotherapy drugs, were determined using CCK-8, Annexin V-FITC/PI and Hoechst 33342 staining assays in vitro. The therapeutic effect of B7-H3 knockdown in combination with chemotherapy drugs were also studied by U937 xenograft models in vivo. Results: B7-H3 mRNA was widely expressed in the 12 hematologic malignancy cell lines except for CZ1 and PB MNCs of volunteers. But the protein level of B7-H3 was only abnormally overexpressed in 12 hematologic malignancy cell lines except for CZ1, with subcellular localizations in nucleus and cytoplasm mostly determined. The down-regulation of B7-H3 in U937 cells significantly decreased cell growth and the rate of colony formation by 32.8% in 72 h and 70.3% in 14 d. Mean inhibition rate of tumor growth with B7-H3 knockdown was 59.4%, and expression of both Ki-67 and PCNA in xenografts was significantly reduced. After B7-H3 silencing, U937 cell cycle was arrested at G0/G1 phase, and the cell cycle-related proteins Cyclin D1 and CDK4 were lower. Cell migration rate of B7-H3 knockdown cells was reduced more than five-fold, and invasion capacity was decreased by 86.7%. The rates of distant metastasis in B7-H3 knockdown xenografts were significantly decreased. The invasion-related proteins MMP-2 and MMP-9 were lower in both B7-H3 knockdown cells and xenografts. B7-H3 RNAi profoundly increased the anti-tumor effect of chemotherapy and enhanced the activity of caspase-3 in vitro and in vivo. At the end of observation (on day 19 after inoculation), inhibition rates of tumor growth in B7-H3 shRNA combined with idarubicin, cytarabine, and idarubicin plus cytarabine groups were 70.5%, 80.0%, and 90.0%, respectively (P=0.006, 0.004 and 0.016). The TUNEL positive cells were significantly increased in the B7-H3 shRNA combined with chemotherapy drugs groups. Conclusions: B7-H3 protein was abnormally overexpressed in 12 hematologic malignancy cell lines except for CZ1, with subcellular localizations in nucleus and cytoplasm mostly determined. B7-H3 may promote U937 cell progression, and shRNA targeting B7-H3 significantly enhances sensitivity to chemotherapeutic drugs. These results may provide new insight into the function of B7-H3 and a promising therapeutic approach targeting B7-H3 in acute monocytic leukemia. Disclosures No relevant conflicts of interest to declare.

scholarly journals Solasonine Suppresses the Proliferation of Acute Monocytic Leukemia Through the Activation of the AMPK/FOXO3A Axis

2021 ◽  
Vol 10 ◽  
Author(s):  
Hong Zhang ◽  
Fang Tian ◽  
Pengjun Jiang ◽  
Shushu Qian ◽  
Xingbin Dai ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Acute Monocytic Leukemia ◽  
Monocytic Leukemia ◽  
Antitumor Effects ◽  
Cycle Arrest ◽  
Compound C ◽  
M Phase

Solasonine, the main active ingredient of Solanum nigrum L., has been reported to exert extensive antitumor activity. However, the antitumor effects in acute monocytic leukemia and the exact mechanisms involved are unknown. In this study, we investigated the role of solasonine on inhibiting the progression of acute monocytic leukemia. Our findings showed that solasonine inhibited the proliferation of acute monocytic leukemic cell lines (THP-1 and MV4-11) in vitro. Solasonine promoted apoptosis and induced cell cycle arrest in the G2/M phase. Analysis of RNA-seq data suggested that solasonine correlated with increased expression of genes in the AMPK/FOXO3A pathway. Inhibition of AMPK with compound C followed by treatment with solasonine showed that solasonine reduced apoptosis, caused less cell cycle arrest, and inactivated the AMPK/FOXO3A axis in THP-1 and MV4-11 cells. Solasonine also inhibited tumor growth by the activation of the AMPK/FOXO3A axis. In conclusion, solasonine inhibited the progress of acute monocytic leukemia in vitro and in vivo and triggered the apoptosis and cell cycle arrest in the G2/M phase by upregulating the AMPK/FOXO3A pathway.

Candida tropicalis Arthritis of the Knee in a Patient with Acute Monocytic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3867-3867
Author(s):  
Jingsong He ◽  
Xiujin Ye ◽  
Weiyan Zheng ◽  
Wenjun Wu ◽  
Maofang Lin ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Candida Tropicalis ◽  
Hematological Malignancy ◽  
Fungal Infections ◽  
Recovery Period ◽  
Leukemic Cells ◽  
Acute Monocytic Leukemia ◽  
Monocytic Leukemia ◽  
Fungal Arthritis

Abstract The patients with malignant hematopathy are the high-risk group of invasive fungal infections (IFI). Candidemia and IFI caused by Candidas in patients with a hematological malignancy are common but Candida arthritis is rare. Here, we reported a case of Candida tropicalis arthritis of the knee that occurred with acute monocytic leukemia during the recovery period of post chemotherapy myelosuppression and agranulocytosis. Case report: A 45-year-old Chinese woman was diagnosed with acute monocytic leukemia with normal caryotype in november 2004. Complete remission was achieved upon completion of 2 courses of induction chemotherapy. Treatment was administered via a Hickman catheter in the left elbow. Two days after phase V consolidation chemotherapy, the patient experienced high fever accompanied by the development of arthritis in the right knee. The diagnosis of Candida tropicalis arthritis of the knee was confirmed by the appearance of Candida tropicalis isolated from the synovial fluid, but no leukemic cells and acid-fast bacilli were found. According to the susceptibility test in vitro, itraconazole and amphotericin B injection were used sequentially for therapy for 4–5 weeks, which effectively inhibited bacterial growth. However, the arthritis relapsed after 4–6 weeks of drug withdrawal. The arthritis was fully resolved after 8 weeks of therapy with fluconazol injection at a dose of 400mg/d and douching articular cavity with amphotericin B once a week. And then sequential therapy with oral fluconazole was commenced. There was no any adverse effect occurrence during the course of treatment. Discussion: Although Candida arthritis in patient with a hematological malignancy is rare, it still occurred in patient with hypoimmunity. Early diagnosis is difficult due to no distinctive clinical manifestation and hysteresis of pathogenic organism detection. It was found that the knee was the sole joint affected according to the review of fourteen other reports of Candida arthritis in patients with a hematological malignancy but the reason remains unclear. Fungal arthritis must be taken into consideration when dealing with patients with immune deficiency accompanied by arthritis, especially gonarthritis. We emphasize that the most important factors for the successful treatment of fungal arthritis are identified diagnosis and adequate dosage through out the course of treatment.

Effect of moderate hypothermia on gene expression by THP-1 cells: a DNA microarray study

2006 ◽  
Vol 26 (1) ◽  
pp. 91-98 ◽  
Author(s):  
Larry A. Sonna ◽  
Matthew M. Kuhlmeier ◽  
Heather C. Carter ◽  
Jeffrey D. Hasday ◽  
Craig M. Lilly ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Geometric Mean ◽  
Acute Monocytic Leukemia ◽  
Moderate Hypothermia ◽  
Binding Motif ◽  
Monocytic Leukemia ◽  
Paired Samples

The mechanisms by which moderate hypothermia (32°C for 12–72 h) affect human cellular function are unclear. We tested the hypothesis that it produces broad changes in mRNA expression in vitro. Acute monocytic leukemia (THP-1) cells were incubated under control conditions (37°C) or moderate hypothermia (32°C) for 24 h. RNA was extracted, and the hypothermic response was confirmed by examining the expression of the cold-induced RNA-binding protein (CIRBP) gene by RT-PCR. Gene expression analysis was performed on seven sets of paired samples with Affymetrix U133A chips using established statistical methods. Sequences were considered affected by cold if they showed statistically significant changes in expression and also met published post hoc filter criteria (changes in geometric mean expression of ≥2-fold and expression calls of “present” or “marginal” in at least half of the experiments). Changes in the expression of selected sequences were further confirmed by PCR. Sixty-seven sequences met the criteria for increased expression (including cold-inducible genes CIRBP and RNA binding motif 3), and 100 sequences showed decreased expression as a result of hypothermia. Functional categories affected by hypothermia included genes involved in immune responses; cell growth, proliferation, and differentiation; and metabolism and biosynthesis. Several heat shock proteins (HSPs) showed decreases in expression. Moderate hypothermia produces substantial changes in gene expression, in categories potentially of systemic importance. Cold exposure without rewarming decreased the expression of several HSPs. These in vitro findings suggest that prolonged hypothermia in vivo might be capable of producing physiologically relevant changes in gene expression by circulating leukocytes.

scholarly journals Therapeutic effects of sesamolin on leukemia induced by WEHI-3B in model mice

2021 ◽  
Vol 64 (1) ◽  
Author(s):  
Senthil Nagarajan ◽  
Jae Kwon Lee
Keyword(s):  
Nk Cell ◽  
Neoplastic Cell ◽  
Positive Control ◽  
Cytolytic Activity ◽  
Leukemic Cells ◽  
Therapeutic Effects ◽  
Control Drug ◽  
Lysis Activity

AbstractSesamolin is one of the lignans derived from sesame oil. It has demonstrated significant antioxidant, anti-aging, and anti-mutagenic properties. It also reportedly augments natural killer (NK) cell lysis activity. We previously reported that sesamolin also exerts anticancer effects in vitro and induces enhanced NK cell cytolytic activity against tumor cells. Herein, we aimed to determine the mechanism by which sesamolin prevents and retards tumorigenesis in BALB/c mouse models of leukemia induced by murine (BALB/c) myelomonocytic leukemia WEHI-3B cells. Banded neutrophils, myeloblasts, and monocytic leukemic cells were more abundant in the leukemia model than in normal mice. Sesamolin decreased the number of leukemic cells by almost 60% in the leukemia model mice in vivo; additionally, sesamolin and the positive control drug, vinblastine, similarly hindered neoplastic cell proliferation. Spleen samples were ~ 4.5-fold heavier in leukemic mice than those obtained from normal mice, whereas spleen samples obtained from leukemic mice treated with sesamolin had a similar weight to those of normal mice. Moreover, sesamolin induced a twofold increase in the cytotoxic activity of leukemic mouse NK cells against WEHI-3B cells. These results indicated that sesamolin exerts anti-leukemic effects in vivo.

In vitro all-trans retinoic acid sensitivity of acute promyelocytic leukemia blasts: a novel indicator of poor patient outcome

Blood ◽  
2001 ◽  
Vol 98 (9) ◽  
pp. 2862-2864 ◽  
Author(s):  
Bruno Cassinat ◽  
Sylvie Chevret ◽  
Fabien Zassadowski ◽  
Nicole Balitrand ◽  
Isabelle Guillemot ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Leukemic Cells ◽  
Event Free Survival ◽  
Free Survival ◽  
Acid Sensitivity ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Acute promyelocytic leukemia (APL) blasts possess a unique sensitivity to the differentiating effects of all-transretinoic acid (ATRA). Multicenter trials confirm that the combination of differentiation and cytotoxic therapy prolongs survival in APL patients. However relapses still occur, and exquisite adaptation of therapy to prognostic factors is essential to aim at a possible cure of the disease. A heterogeneity was previously reported in the differentiation rate of patients' APL blasts, and it was postulated that this may reflect the in vivo heterogeneous outcome. In this study, it is demonstrated that patients of the APL93 trial whose leukemic cells achieved optimal differentiation with ATRA in vitro at diagnosis had a significantly improved event-free survival (P = .01) and lower relapse rate (P = .04). This analysis highlights the importance of the differentiation step in APL therapy and justifies ongoing studies aimed at identifying novel RA-differentiation enhancers.

Differentiation arrest and stromal cell-independent growth of murine erythroleukemia cells are associated with elevated expression of ets-related genes but not with mutation of p53

1993 ◽  
Vol 13 (9) ◽  
pp. 5582-5592
Author(s):  
R J Nibbs ◽  
K Itoh ◽  
W Ostertag ◽  
P R Harrison
Keyword(s):  
Stromal Cells ◽  
Stromal Cell ◽  
Gene Activation ◽  
Leukemic Cells ◽  
Term Survival ◽  
Elevated Expression ◽  
D Cells ◽  
Murine Erythroleukemia

The ELM erythroleukemia is novel in that long-term survival of leukemic cells in culture (ELM-D cells) is dependent on contact with a bone marrow-derived stromal feeder cell layer. However, a number of stroma-independent (ELM-I) mutants that vary in their ability to differentiate in vitro in response to erythropoietin and interleukin-3 have been derived. We have attempted to define the genetic changes responsible for these different phenotypes. At the p53 locus in the primary leukemic cells, one copy of the gene has been lost whereas the other contains an 18-bp depletion, implicating its mutation as an early step in the development of the leukemia. Changes in ets gene expression have also been found. The Fli-1 gene region is rearranged in the primary tumor because of the insertion of a retrovirus inserted upstream of one Fli-1 allele, but this does not result in Fli-1 gene activation in any of the ELM-D or ELM-I cell lines except one. It seems significant that this line is the only one to have lost the ability to differentiate in response to erythropoietin. In addition, up-regulation of erg is associated with stromal cell-independent growth, since all ELM-I mutants have moderate levels of erg mRNA, whereas only low or undetectable levels are found in primary leukemic cells in vivo or in ELM-D cells in vitro. This up-regulation of erg mRNA seems to be important for stromal cell-independent growth, since ELM-D cells show elevated expression of the erg gene after separation from stromal cells. This seems to be made permanent in ELM-I mutants, since they do not down-regulate erg mRNA when grown in contact with stromal cells. We therefore propose that ets family members regulate both the survival and differentiation of erythroid cells.

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