scholarly journals Functional changes in human leukemic cell line HL-60. A model for myeloid differentiation

1979 ◽  
Vol 82 (2) ◽  
pp. 315-322 ◽  
Author(s):  
PE Newburger ◽  
ME Chovaniec ◽  
JS Greenberger ◽  
HJ Cohen
Keyword(s):  
Cell Line ◽  
Leukemia Cell ◽  
Leukemic Cell ◽  
Leukemia Cell Line ◽  
Bacterial Killing ◽  
Functional Changes ◽  
Myeloid Development ◽  
Human Leukemic Cell Line ◽  
Time Required ◽  
Morphologic Type

Polar solvents induce terminal differentiation in the human promyelocytic leukemia cell line HL-60. The present studies describe the functional changes that accompany the morphologic progression from promyelocytes to bands and poly-morphonuclear leukocytes (PMN) over 9 d of culture in 1.3 percent dimethylsulfoxide (DMSO). As the HL-60 cells mature, the rate of O(2-) production increase 18-fold, with a progressive shortening of the lag time required for activation. Hexosemonophosphate shunt activity rises concomitantly. Ingestin of paraffin oil droplets opsonized with complement or Ig increases 10-fold over 9 d in DMSO. Latex ingestion per cell by each morphologic type does not change significantly, but total latex ingestion by groups of cells increases with the rise in the proportion of mature cells with greater ingestion capacities. Degranulation, as measured by release of β-glucuronidase, lysozyme, and peroxidase, reaches maximum after 3-6 d in DMSO, then declines. HL-60 cells contain no detectable lactoferrin, suggesting that their secondary granules are absent or defective. However, they kill staphylococci by day 6 in DMSO. Morphologically immature cells (days 1-3 in DMSO) are capable of O(2-) generation, hexosemonophosphate shunt activity, ingestion, degranulation, and bacterial killing. Maximal performance of each function by cells incubated in DMSO for longer periods of time is 50-100 percent that of normal PMN. DMSO- induced differentiation of HL-60 cells is a promising model for myeloid development.

scholarly journals Establishment and characterization of an erythropoietin-dependent subline, UT-7/Epo, derived from human leukemia cell line, UT-7

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 456-464 ◽  
Author(s):  
N Komatsu ◽  
M Yamamoto ◽  
H Fujita ◽  
A Miwa ◽  
K Hatake ◽  
...  
Keyword(s):  
Cell Line ◽  
Leukemia Cell ◽  
Leukemic Cell ◽  
Leukemia Cell Line ◽  
Positive Staining ◽  
Human Leukemia ◽  
Gm Csf ◽  
Human Leukemia Cell Line ◽  
Macrophage Colony ◽  
Human Leukemic Cell Line

UT-7 is a human leukemic cell line capable of growing in interleukin-3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF), or erythropoietin (Epo) (Komatsu et al, Cancer Res 51:341, 1991). To study the effect of Epo on proliferation and differentiation of UT-7, we maintained the UT-7 cell culture for more than 6 months in the presence of Epo. As a result, a subline, UT-7/Epo, was established. The growth of UT-7/Epo could be supported by Epo but not by GM-CSF or IL-3. UT- 7/Epo showed a greater level of heme content and ratio of benzidine- positive staining cells than did UT-7. Butyric acid promoted the synthesis of hemoglobin in UT-7/Epo, but not UT-7. Further, the mRNA concentrations of the c-myb oncogene and GM-CSF receptor beta-subunit were decreased substantially in UT-7/Epo cells. These findings showed that UT-7/Epo cells had progressed further in erythroid development than UT-7 cells, and suggested that long-term culture in Epo had promoted this differentiation. Whereas availability of the Epo receptor (Epo-R) for binding of Epo was reduced in UT-7/Epo cells compared with UT-7 cells, the Epo-R showed a similar affinity for Epo. This observation suggested that change(s) in postreceptor signaling step might be involved in the establishment and maintenance of the UT-7/Epo phenotype.

scholarly journals Inhibitor of hematopoietic cell proliferation derived from a human leukemic cell line

Blood ◽  
1978 ◽  
Vol 52 (1) ◽  
pp. 143-152
Author(s):  
T Olofsson ◽  
MJ Cline
Keyword(s):  
Cell Proliferation ◽  
Cell Line ◽  
Leukemia Cell ◽  
Direct Interaction ◽  
Leukemic Cell ◽  
Hematopoietic Cell ◽  
Leukemia Cell Line ◽  
Target Cells ◽  
Cell Cycle Inhibition ◽  
Human Leukemic Cell Line

A continuously growing human myeloid leukemia cell line (K562) produced a potent high-molecular-weight inhibitor of hematopoietic cell proliferation. It was most active against myeloid stem cells (CFU-C) and proliferating T lymphocytes; it was less active against erythroid precursors (CFU-E) and did not inhibit fibroblasts or established lines of epithelioid cells or B lymphocytes. Inhibition of CFU-C was by direct interaction rather than by modulation of production of colony- stimulating activity and probably occurred at restricted points in the cell cycle. Inhibition could, within limits, be reversed by washing the target cells. Production of inhibitors of hematopoiesis is not a general property of established cell lines, and only two have thus far been identified in screening of 30 such lines.

scholarly journals Inhibitor of hematopoietic cell proliferation derived from a human leukemic cell line

Blood ◽  
1978 ◽  
Vol 52 (1) ◽  
pp. 143-152 ◽  
Author(s):  
T Olofsson ◽  
MJ Cline
Keyword(s):  
Cell Proliferation ◽  
Cell Line ◽  
Leukemia Cell ◽  
Direct Interaction ◽  
Leukemic Cell ◽  
Hematopoietic Cell ◽  
Leukemia Cell Line ◽  
Target Cells ◽  
Cell Cycle Inhibition ◽  
Human Leukemic Cell Line

Abstract A continuously growing human myeloid leukemia cell line (K562) produced a potent high-molecular-weight inhibitor of hematopoietic cell proliferation. It was most active against myeloid stem cells (CFU-C) and proliferating T lymphocytes; it was less active against erythroid precursors (CFU-E) and did not inhibit fibroblasts or established lines of epithelioid cells or B lymphocytes. Inhibition of CFU-C was by direct interaction rather than by modulation of production of colony- stimulating activity and probably occurred at restricted points in the cell cycle. Inhibition could, within limits, be reversed by washing the target cells. Production of inhibitors of hematopoiesis is not a general property of established cell lines, and only two have thus far been identified in screening of 30 such lines.

scholarly journals Establishment and characterization of an erythropoietin-dependent subline, UT-7/Epo, derived from human leukemia cell line, UT-7

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 456-464 ◽  
Author(s):  
N Komatsu ◽  
M Yamamoto ◽  
H Fujita ◽  
A Miwa ◽  
K Hatake ◽  
...  
Keyword(s):  
Cell Line ◽  
Leukemia Cell ◽  
Leukemic Cell ◽  
Leukemia Cell Line ◽  
Positive Staining ◽  
Human Leukemia ◽  
Gm Csf ◽  
Human Leukemia Cell Line ◽  
Macrophage Colony ◽  
Human Leukemic Cell Line

Abstract UT-7 is a human leukemic cell line capable of growing in interleukin-3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF), or erythropoietin (Epo) (Komatsu et al, Cancer Res 51:341, 1991). To study the effect of Epo on proliferation and differentiation of UT-7, we maintained the UT-7 cell culture for more than 6 months in the presence of Epo. As a result, a subline, UT-7/Epo, was established. The growth of UT-7/Epo could be supported by Epo but not by GM-CSF or IL-3. UT- 7/Epo showed a greater level of heme content and ratio of benzidine- positive staining cells than did UT-7. Butyric acid promoted the synthesis of hemoglobin in UT-7/Epo, but not UT-7. Further, the mRNA concentrations of the c-myb oncogene and GM-CSF receptor beta-subunit were decreased substantially in UT-7/Epo cells. These findings showed that UT-7/Epo cells had progressed further in erythroid development than UT-7 cells, and suggested that long-term culture in Epo had promoted this differentiation. Whereas availability of the Epo receptor (Epo-R) for binding of Epo was reduced in UT-7/Epo cells compared with UT-7 cells, the Epo-R showed a similar affinity for Epo. This observation suggested that change(s) in postreceptor signaling step might be involved in the establishment and maintenance of the UT-7/Epo phenotype.

Antiproliferative Effects of a Series of Cyclic Imides on Primary Endothelial Cells and a Leukemia Cell Line

2008 ◽  
Vol 63 (9-10) ◽  
pp. 675-680 ◽  
Author(s):  
José A. Yunes ◽  
Angelo A. Cardoso ◽  
Rosendo A. Yunes ◽  
Rogério Corrêa ◽  
Fátima de Campos-Buzzi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cytotoxic Activity ◽  
Cell Line ◽  
Umbilical Vein ◽  
Leukemia Cell ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Leukemia Cell Line ◽  
Cyclic Imides ◽  
Umbilical Vein Endothelial Cells

The present study describes the cytotoxic properties of a series of 15 cyclic imides observed against different endothelial cells and K562 leukemic cells. Initially, eight structurally unrelated compounds were evaluated against cultured bone marrow endothelial cells (BMEC) and human umbilical vein endothelial cells (HUVEC). Only two imides showed cytotoxic activity at 10 μm. In continuation of our screening, eight compounds, structurally related to the compound with the higher cytotoxic activity, were assayed against endothelial cells and the K562 leukemic cell line. All of these new compounds except two exhibited cytotoxic and antiproliferative activities at concentrations below 10 μm against BMEC and HUVEC, respectively. The K562 leukemia cell line was only affected by concentrations of 100 μm. Preliminary SAR analysis indicated that the cytotoxic activity of these compounds was related to the presence of a planar imide ring directly bound to an aromatic ring.

scholarly journals CRISPR-Cas9 Editing of Human Histone Deubiquitinase Gene USP16 in Human Monocytic Leukemia Cell Line THP-1

2021 ◽  
Vol 9 ◽  
Author(s):  
Iveta Gažová ◽  
Lucas Lefevre ◽  
Stephen J. Bush ◽  
Rocio Rojo ◽  
David A. Hume ◽  
...  
Keyword(s):  
Cell Line ◽  
Leukemia Cell ◽  
Leukemic Cell ◽  
Leukemia Cell Line ◽  
Acute Monocytic Leukemia ◽  
Wild Type ◽  
Monocytic Leukemia ◽  
Damage Repair ◽  
Apparent Loss

USP16 is a histone deubiquitinase which facilitates G2/M transition during the cell cycle, regulates DNA damage repair and contributes to inducible gene expression. We mutated the USP16 gene in a high differentiation clone of the acute monocytic leukemia cell line THP-1 using the CRISPR-Cas9 system and generated four homozygous knockout clones. All were able to proliferate and to differentiate in response to phorbol ester (PMA) treatment. One line was highly proliferative prior to PMA treatment and shut down proliferation upon differentiation, like wild type. Three clones showed sustained expression of the progenitor cell marker MYB, indicating that differentiation had not completely blocked proliferation in these clones. Network analysis of transcriptomic differences among wild type, heterozygotes and homozygotes showed clusters of genes that were up- or down-regulated after differentiation in all cell lines. Prior to PMA treatment, the homozygous clones had lower levels than wild type of genes relating to metabolism and mitochondria, including SRPRB, encoding an interaction partner of USP16. There was also apparent loss of interferon signaling. In contrast, a number of genes were up-regulated in the homozygous cells compared to wild type at baseline, including other deubiquitinases (USP12, BAP1, and MYSM1). However, three homozygotes failed to fully induce USP3 during differentiation. Other network clusters showed effects prior to or after differentiation in the homozygous clones. Thus the removal of USP16 affected the transcriptome of the cells, although all these lines were able to survive, which suggests that the functions attributed to USP16 may be redundant. Our analysis indicates that the leukemic line can adapt to the extreme selection pressure applied by the loss of USP16, and the harsh conditions of the gene editing and selection protocol, through different compensatory pathways. Similar selection pressures occur during the evolution of a cancer in vivo, and our results can be seen as a case study in leukemic cell adaptation. USP16 has been considered a target for cancer chemotherapy, but our results suggest that treatment would select for escape mutants that are resistant to USP16 inhibitors.

scholarly journals Establishment of a human acute myeloid leukemia cell line (Kasumi-1) with 8;21 chromosome translocation

Blood ◽  
1991 ◽  
Vol 77 (9) ◽  
pp. 2031-2036 ◽  
Author(s):  
H Asou ◽  
S Tashiro ◽  
K Hamamoto ◽  
A Otsuji ◽  
K Kita ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Line ◽  
Myeloid Leukemia ◽  
Leukemia Cell ◽  
Leukemic Cell ◽  
Chromosome Translocation ◽  
Leukemia Cell Line ◽  
Gm Csf ◽  
Human Acute Myeloid Leukemia ◽  
Acute Myeloid

Abstract A novel leukemic cell line with an 8;21 chromosome translocation, designated as Kasumi-1, was established from the peripheral blood of a 7-year-old boy suffering from acute myeloid leukemia (AML). The Kasumi- 1 cells were positive for myeloperoxidase showing a morphology of myeloid maturation. The response in proliferation assay was observed in the culture with interleukin-3 (IL-3), IL-6, granulocyte colony- stimulating factor (G-CSF), and granulocytemacrophage CSF (GM-CSF), but not with IL-1 or IL-5. Neither granulocytic nor eosinophilic maturation was observed in the liquid culture by the addition of dimethyl sulfoxide, G-CSF, or IL-5, respectively. In contrast, induction of macrophagelike cells was seen by the addition of phorbol ester. This is the first report of a human AML cell line with t(8;21) that has characteristics of myeloid and macrophage lineages. The cell line could be a useful tool for elucidating the pathophysiology of AML with t(8;21).

scholarly journals Apoptotic Effect of Boron Derivatives on HL-60 Acute Promyelocytic Leukemia Cell Line

Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1533
Author(s):  
Tuğba Erkmen ◽  
Belgin Sert Serdar ◽  
Halil Ateş ◽  
Mehmet Korkmaz ◽  
Semra Koçtürk
Keyword(s):  
Cell Line ◽  
Wide Spectrum ◽  
Leukemia Cell ◽  
Young Patients ◽  
Leukemic Cell ◽  
Leukemia Cell Line ◽  
Therapeutic Approaches ◽  
Boron Compounds ◽  
Apoptotic Effect ◽  
Promyelocytic Leukemia Cell Line

Acute myeloid leukemia (AML) is the most common form of acute leukemia and the overall 5-year survival in AML patients is 40–45% in young patients and less than 10% in elderly patients. Therefore, there is still a need to improve therapeutic approaches. After development of boron-based anticancer drugs (such as Bortezomib), boron compounds have gained attention with possible anti-leukemic feature. In this study, we evaluated anti-tumoral effects of borax pentahydrate (BP) and disodium pentaborate decahydrate (DPD) on leukemic cell line (HL-60). Cell viability was assessed by MTT assay and apoptotic effect of the compounds were evaluated by flow cytometry and cleaved PARP level detection by western blot. We observed that BP (24 mM) and DPD (6 mM) exhibit anti-leukemic effect via induction of apoptosis. Our study suggest that BP and DPD have potential anti-leukemic effect, which needs to be confirmed by further wide-spectrum studies.

Charcterization of a Newly Established Megakaryo/Erythroid Leukemia Cell Line, JAS-R.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4327-4327
Author(s):  
Hisashi Yamada ◽  
Junko Horiguchi-Yamada ◽  
Tetsuaki Sekikawa
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Leukemia Cell ◽  
Leukemic Cell ◽  
Neutralizing Antibody ◽  
Chromosome Analysis ◽  
Erythropoietin Receptor ◽  
Leukemia Cell Line ◽  
Erythroid Cell ◽  
Leukemic Cell Lines

Abstract A few leukemic cell lines which express megakaryo/erythroid markers are available. We recently established a new cell line, designated JAS-R, from a 64-year-old patient with acute megakaryocytic leukemia (AML M7). Immunophenotyping showed that JAS-R cells were positive for CD4, CD7, CD13, CD33, CD41, CD61 and glycophorin A. Chromosome analysis was composite karyotype, but no major translocation abnormalities were observed. Electron-microscope examination disclosed that JAS-R had bleb like surface margin and a-granules in cytoplasm. Major four proteins which exist in a-granule were expressed high levels in JAS-R by RT-PCR. To further characterize JAS-R from four other megakaryo/erythroid cell lines (MEG-01, CMK, K562 and KU812), the comparison of gene expression profiling was studied by using oligo-DNA array. JAS-R was categorized as most different cell line among them. Of note, JAS-R secreted erythropoietin and expressed erythropoietin-receptor. But erythropoietin-neutralizing antibody failed to inhibit the growth of JAS-R cells. JAS-R may be useful for the further understanding of megakaryo and erythroid regulation and for the study of megakaryo/erythroid leukemogenesis.

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