scholarly journals Characterization of the continuous, differentiating myeloid cell line (HL-60) from a patient with acute promyelocytic leukemia

Blood ◽  
1979 ◽  
Vol 54 (3) ◽  
pp. 713-733 ◽  
Author(s):  
R Gallagher ◽  
S Collins ◽  
J Trujillo ◽  
K McCredie ◽  
M Ahearn ◽  
...  
Keyword(s):  
Cell Line ◽  
Acute Promyelocytic Leukemia ◽  
Cultured Cells ◽  
Light And Electron Microscopy ◽  
Myeloid Cell ◽  
Promyelocytic Leukemia ◽  
Lymphoid Cells ◽  
Complement C3 ◽  
Semisolid Medium ◽  
Myeloid Cell Line

In a prelminary communication, we described the establishment of a continuous human myeloid cell line (HL-60). Here we report the detailed properties of this cell line and document its derivation from the peripheral blood leukocytes of a patient with acute promyelocytic leukemia. As characterized by light and electron microscopy, the predominant cell type in both the fresh and cultured sources is a neutrophilic promyelocyte with prominent nuclear/cytoplasmic asynchrony. Up to 10% of the cultured cells spontaneously differentiate beyond the promyelocyte stage, and the proportion of terminally differentiated cells is markedly enhanced by compounds known to stimulate differentiation of mouse (Friend) erythroleukemia cells. The HL-60 cells lack specific markers for lymphoid cells, but express surface receptors for Fc fragment and complement (C3), which have been associated with differentiated granulocytes. They exhibit phagocytic activity and responsiveness to a chemotactic stimulus commensurate with the proportion of mature cells. As characteristic of transformed cells, the HL-60 cells form colonies in semisolid medium and produce subcutaneous myeloid tumors (chloromas) in nude mice. A source of colony-stimulating activity stimulated the cloning efficiency in soft agar 5--30-fold. Despite adaptations to culture, the morphological phenotype and responsiveness to chemical induction of differentiation is essentially unchanged through at least 85 passages. Cytogenetic studies reveal aneuploidy. Metaphases with 44 chromosomes predominated in vivo and in early culture passages; however, clones with 45 or 46 chromosomes became predominant with continued passaging. The most consistent karyotypic abnormalities were the deletion of chromosomes 5, 8, and X and the addition of a marker resembling a D-group acrocentric and of a submetacentric marker, most likely an abnormal E-group chromosome. No DNA herpesvirus or RNA retrovirus was isolated in the fresh or cultured cells. The HL-60 cultured cell line provides a continuous source of human cells for studying the molecular events of myeloid differentiation and the effects of physiologic, pharmacologic, and virologic elements on this process.

scholarly journals Characterization of the continuous, differentiating myeloid cell line (HL-60) from a patient with acute promyelocytic leukemia

Blood ◽  
1979 ◽  
Vol 54 (3) ◽  
pp. 713-733 ◽  
Author(s):  
R Gallagher ◽  
S Collins ◽  
J Trujillo ◽  
K McCredie ◽  
M Ahearn ◽  
...  
Keyword(s):  
Cell Line ◽  
Acute Promyelocytic Leukemia ◽  
Cultured Cells ◽  
Light And Electron Microscopy ◽  
Myeloid Cell ◽  
Promyelocytic Leukemia ◽  
Lymphoid Cells ◽  
Complement C3 ◽  
Semisolid Medium ◽  
Myeloid Cell Line

Abstract In a prelminary communication, we described the establishment of a continuous human myeloid cell line (HL-60). Here we report the detailed properties of this cell line and document its derivation from the peripheral blood leukocytes of a patient with acute promyelocytic leukemia. As characterized by light and electron microscopy, the predominant cell type in both the fresh and cultured sources is a neutrophilic promyelocyte with prominent nuclear/cytoplasmic asynchrony. Up to 10% of the cultured cells spontaneously differentiate beyond the promyelocyte stage, and the proportion of terminally differentiated cells is markedly enhanced by compounds known to stimulate differentiation of mouse (Friend) erythroleukemia cells. The HL-60 cells lack specific markers for lymphoid cells, but express surface receptors for Fc fragment and complement (C3), which have been associated with differentiated granulocytes. They exhibit phagocytic activity and responsiveness to a chemotactic stimulus commensurate with the proportion of mature cells. As characteristic of transformed cells, the HL-60 cells form colonies in semisolid medium and produce subcutaneous myeloid tumors (chloromas) in nude mice. A source of colony-stimulating activity stimulated the cloning efficiency in soft agar 5--30-fold. Despite adaptations to culture, the morphological phenotype and responsiveness to chemical induction of differentiation is essentially unchanged through at least 85 passages. Cytogenetic studies reveal aneuploidy. Metaphases with 44 chromosomes predominated in vivo and in early culture passages; however, clones with 45 or 46 chromosomes became predominant with continued passaging. The most consistent karyotypic abnormalities were the deletion of chromosomes 5, 8, and X and the addition of a marker resembling a D-group acrocentric and of a submetacentric marker, most likely an abnormal E-group chromosome. No DNA herpesvirus or RNA retrovirus was isolated in the fresh or cultured cells. The HL-60 cultured cell line provides a continuous source of human cells for studying the molecular events of myeloid differentiation and the effects of physiologic, pharmacologic, and virologic elements on this process.

AZT Incorporation into Mitochondria: Study in a Human Myeloid Cell Line

1996 ◽  
Vol 15 (5) ◽  
pp. 363-366 ◽  
Author(s):  
NEIL J. NUSBAUM ◽  
PHILLIP E. JOSEPH
Keyword(s):  
Cell Line ◽  
Myeloid Cell ◽  
Myeloid Cell Line

Ruthenium metallodendrimers with anticancer potential in an acute promyelocytic leukemia cell line (HL60)

2017 ◽  
Vol 87 ◽  
pp. 39-47 ◽  
Author(s):  
Sylwia Michlewska ◽  
Maksim Ionov ◽  
Dzmitry Shcharbin ◽  
Marta Maroto-Díaz ◽  
Rafael Gomez Ramirez ◽  
...  
Keyword(s):  
Cell Line ◽  
Acute Promyelocytic Leukemia ◽  
Leukemia Cell ◽  
Promyelocytic Leukemia ◽  
Leukemia Cell Line ◽  
Acute Promyelocytic Leukemia Cell ◽  
Promyelocytic Leukemia Cell Line

scholarly journals Detailed molecular cytogenetic characterisation of the myeloid cell line U937 reveals the fate of homologous chromosomes and shows that centromere capture is a feature of genome instability

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Ruth N. MacKinnon ◽  
Joanne Peverall ◽  
Lynda J. Campbell ◽  
Meaghan Wall
Keyword(s):  
Cell Line ◽  
Chromosome Pair ◽  
Fusion Gene ◽  
Genome Instability ◽  
Snp Array ◽  
Myeloid Cell ◽  
Chromosome 20 ◽  
Myeloid Cell Line ◽  
Multicolour Fish ◽  
Chromosome Segments

Abstract Background The U937 cell line is widely employed as a research tool. It has a complex karyotype. A PICALM-MLLT10 fusion gene formed by the recurrent t(10;11) translocation is present, and the myeloid common deleted region at 20q12 has been lost from its near-triploid karyotype. We carried out a detailed investigation of U937 genome reorganisation including the chromosome 20 rearrangements and other complex rearrangements. Results SNP array, G-banding and Multicolour FISH identified chromosome segments resulting from unbalanced and balanced rearrangements. The organisation of the abnormal chromosomes containing these segments was then reconstructed with the strategic use of targeted metaphase FISH. This provided more accurate karyotype information for the evolving karyotype. Rearrangements involving the homologues of a chromosome pair could be differentiated in most instances. Centromere capture was demonstrated in an abnormal chromosome containing parts of chromosomes 16 and 20 which were stabilised by joining to a short section of chromosome containing an 11 centromere. This adds to the growing number of examples of centromere capture, which to date have a high incidence in complex karyotypes where the centromeres of the rearranged chromosomes are identified. There were two normal copies of one chromosome 20 homologue, and complex rearrangement of the other homologue including loss of the 20q12 common deleted region. This confirmed the previously reported loss of heterozygosity of this region in U937, and defined the rearrangements giving rise to this loss. Conclusions Centromere capture, stabilising chromosomes pieced together from multiple segments, may be a common feature of complex karyotypes. However, it has only recently been recognised, as this requires deliberate identification of the centromeres of abnormal chromosomes. The approach presented here is invaluable for studying complex reorganised genomes such as those produced by chromothripsis, and provides a more complete picture than can be obtained by microarray, karyotyping or FISH studies alone. One major advantage of SNP arrays for this process is that the two homologues can usually be distinguished when there is more than one rearrangement of a chromosome pair. Tracking the fate of each homologue and of highly repetitive DNA regions such as centromeres helps build a picture of genome evolution. Centromere- and telomere-containing elements are important to deducing chromosome structure. This study confirms and highlights ongoing evolution in cultured cell lines.

Combined procoagulant activity and proteolytic activity of acute promyelocytic leukemic cells: reversal of the bleeding disorder by cell differentiation

Blood ◽  
1989 ◽  
Vol 73 (3) ◽  
pp. 800-805 ◽  
Author(s):  
PW Wijermans ◽  
VI Rebel ◽  
GJ Ossenkoppele ◽  
PC Huijgens ◽  
MM Langenhuijsen
Keyword(s):  
Cell Differentiation ◽  
Cell Line ◽  
Acute Promyelocytic Leukemia ◽  
Proteolytic Activity ◽  
Fibrinolytic Activity ◽  
Promyelocytic Leukemia ◽  
Procoagulant Activity ◽  
Bleeding Complications ◽  
Monocytic Differentiation ◽  
Elastase Activity

Abstract In the human promyelocytic cell line HL60, we observed both a strong procoagulant activity (PCA) on the cell membrane and proteolytic activity in the lysate of these cells. Because these cell-line cells are susceptible to differentiation to either a more mature granulocytic or monocytic form, we were able to study the hypothesis that the combination of PCA and proteolytic activity is confined to the promyelocyte. This may explain the severe coagulopathy seen in patients with acute promyelocytic leukemia. Cell differentiation in a myeloid direction induced by retinoic acid or DMSO led to a diminished PCA, while not affecting the fibrinolytic activity. On the other hand, monocytic differentiation obtained by culturing the cells in the presence of 1; 25 dihydroxy vitamin D3 led to the complete disappearance of the proteolytic activity of the cell lysate, although the procoagulant activity was still present. Furthermore, we found that the elastase activity almost disappeared after monocytic differentiation. We also studied the PCA, proteolytic activity, and elastase activity of blast cells of patients with acute myeloid leukemia. Only in patients with acute promyelocytic leukemia did we observe both a strong PCA and fibrinolytic activity. This supports our hypothesis that the combination of these activities is unique to the promyelocyte and may explain the observed bleeding complications in patients with acute promyelocytic leukemia.

AM580, a stable benzoic derivative of retinoic acid, has powerful and selective cyto-differentiating effects on acute promyelocytic leukemia cells

Blood ◽  
1996 ◽  
Vol 87 (4) ◽  
pp. 1520-1531 ◽  
Author(s):  
M Gianni ◽  
M Li Calzi ◽  
M Terao ◽  
G Guiso ◽  
S Caccia ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cell Line ◽  
Acute Promyelocytic Leukemia ◽  
Retinoic Acid Receptor ◽  
Chromosomal Translocation ◽  
Promyelocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Stable Phase ◽  
Differentiation Markers

All-trans retinoic acid (ATRA) is successfully used in the cyto- differentiating treatment of acute promyelocytic leukemia (APL). Paradoxically, APL cells express PML-RAR, an aberrant form of the retinoic acid receptor type alpha (RAR alpha) derived from the leukemia- specific t(15;17) chromosomal translocation. We show here that AM580, a stable retinobenzoic derivative originally synthesized as a RAR alpha agonist, is a powerful inducer of granulocytic maturation in NB4, an APL-derived cell line, and in freshly isolated APL blasts. After treatment of APL cells with AM580 either alone or in combination with granulocyte colony-stimulating factor (G-CSF), the compound induces granulocytic maturation, as assessed by determination of the levels of leukocyte alkaline phosphatase, CD11b, CD33, and G-CSF receptor mRNA, at concentrations that are 10- to 100-fold lower than those of ATRA necessary to produce similar effects. By contrast, AM580 is not effective as ATRA in modulating the expression of these differentiation markers in the HL-60 cell line and in freshly isolated granulocytes obtained from the peripheral blood of chronic myelogenous leukemia patients during the stable phase of the disease. In NB4 cells, two other synthetic nonselective RAR ligands are capable of inducing LAP as much as AM580, whereas RAR beta- or RAR gamma-specific ligands are totally ineffective. These results show that AM580 is more powerful than ATRA in modulating the expression of differentiation antigens only in cells in which PML-RAR is present. Binding experiments, using COS-7 cells transiently transfected with PML-RAR and the normal RAR alpha, show that AM580 has a lower affinity than ATRA for both receptors. However, in the presence of PML-RAR, the synthetic retinoid is a much better transactivator of retinoic acid-responsive element-containing promoters than the natural retinoid, whereas, in the presence of RAR alpha, AM580 and ATRA have similar activity. This may explain the strong cyto-differentiating potential of AM580 in PML-RAR-containing leukemic cells.

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