Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome.
TL;DR: This CML cell-line represents a unique source of CML cells with meaningful indicators of malignancy for clinical and experimental studies.
About: This article is published in Blood.The article was published on 1975-03-01. It has received 2774 citations till now. The article focuses on the topics: Chronic myelogenous leukemia & Philadelphia chromosome.
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TL;DR: Since the microculture tetrazolium assay provides sensitive and reproducible indices of growth as well as drug sensitivity in individual cell lines over the course of multiple passages and several months' cultivation, it appears suitable for initial-stage in vitro drug screening.
Abstract: For the past 30 years strategies for the preclinical discovery and development of potential anticancer agents have been based largely upon the testing of agents in mice bearing transplantable leukemias and solid tumors derived from a limited number of murine as well as human sources. The feasibility of implementing an alternate approach, namely combined in vitro/in vivo screening for selective cytotoxicity among panels of human tumor cell lines derived from a broad spectrum of human solid tumors is under investigation. A group of 30 cell lines acquired from a variety of sources and representing 8 lung cancer pathologies as well as 76 cell lines representing 10 other categories of human cancer (carcinomas of colon, breast, kidney, prostate, ovary, head and neck; glioma; leukemia; melanoma; and sarcoma) have exhibited acceptable growth characteristics and suitable colorimetric profiles in a single, standard culture medium. Measurements of in vitro growth in microculture wells by cell-mediated reduction of tetrazolium showed excellent correlation (0.89 less than r2 less than 0.98) with measurements of cellular protein in adherent cell line cultures as well as viable cell count in suspension cell line cultures (0.94 less than r2 less than 0.99). Since the microculture tetrazolium assay provides sensitive and reproducible indices of growth as well as drug sensitivity in individual cell lines over the course of multiple passages and several months' cultivation, it appears suitable for initial-stage in vitro drug screening.
3,098 citations
TL;DR: Results indicate that THP‐1 is a leukemic cell line with distinct monocytic markers, and the ability to restore T‐lymphocyte response to Con A.
Abstract: A human leukemic cell line (THP-1) cultured from the blood of a boy with acute monocytic leukemia is described. This cell line had Fc and C3b receptors, but no surface or cytoplasmic immunoglobulins. HLA haplotypes of THP-1 were HLA-A2, -A9, -B5, -DRW1 and -DRW2. The monocytic nature of the cell line was characterized by: (1) the presence of alpha-naphthyl butyrate esterase activities which could be inhibited by NaF; (2) lysozyme production; (3) the phagocytosis of latex particles and sensitized sheep erythrocytes; and (4) the ability to restore T-lymphocyte response to Con A. The cells did not possess Epstein-Barr virus-associated nuclear antigen. These results indicate that THP-1 is a leukemia cell line with distinct monocytic markers. During culture, THP-1 maintained these monocytic characteristics for over 14 months.
2,209 citations
TL;DR: The derivation from myeloid leukaemic cells of a leukocyte culture is described here for the first time that by morphological and histochemical criteria clearly and persistently differentiates along the myeloids series without an exogenous source of conditioned medium.
Abstract: ATTEMPTS to develop long-term suspension cultures of human myeloid leukaemic cells have met with limited success. Lymphoblastoid lines carrying the Epstein–Barr virus genome occasionally arise during such attempts but these lymphoid cells originate from contaminating B lymphocytes and not from the leukaemic myeloid cells1. A line established from the pleural fluid of a patient with chronic myeloid leukaemia in blast crisis2 (designated K-562) has no B-cell or T-cell markers3–4 and does not seem to be of lymphoid origin4. Its lack of morphological and histochemical differentiation2–4, however, makes it difficult to determine whether these cells are derived from myeloblasts or more primitive stem cells4. Another less documented cell line (8261) derived from the peripheral blood of a patient with acute myelogenous leukaemia showed apparent morphological and functional differentiation in agar in the presence of a feeder layer of peripheral blood leukocytes but did not differentiate in suspension culture5. Our laboratory previously reported that cultures of differentiating myeloid leukaemic cells can be maintained for several months in suspension culture but only when enriched with conditioned media (CM) from certain monolayer fibroblastic cultures of first trimester whole human embryos (ref. 6 and Ruscetti et al. in preparation). We describe here for the first time the derivation from myeloid leukaemic cells of a leukocyte culture that by morphological and histochemical criteria clearly and persistently differentiates along the myeloid series without an exogenous source of conditioned medium.
2,115 citations
TL;DR: This study suggests that retinoids could provide a therapeutic tool in the treatment of acute myeloid leukemia, and indicates thatretinoids, in addition to their well-characterized involvement in epithelial cell differentiation, may also be involved in the differentiation of certain hematopoietic cells.
Abstract: The HL-60 cell line, derived from a patient with acute promyelocytic leukemia, proliferates continuously in suspension culture and consists predominantly (greater than 90%) of promyelocytes. These cells can be induced to differentiate to morphologically and functionally mature granulocytes by incubation with a wide variety of compounds, including butyrate and hypoxanthine and polar planar compounds such as dimethyl sulfoxide and hexamethylene bisacetamide. We have now found that retinoic acid (all-trans-retinoic acid) induces differentiation (as measured morphologically and by the ability to reduce nitroblue tetrazolium) of HL-60 at concentrations as low as 1 nM. Maximal differentiation (approximately 90%) occurs at 1 micro M, a concentration 1/500th to 1/160,000th the concentrations of butyrate (0.5 mM) and dimethyl sulfoxide (160 mM) that promote a similar increase in differentiation. Continuous exposure to retinoic acid is necessary for optimal differentiation, with the percentage of mature cells in the culture directly related to the length of time of exposure to retinoic acid. Retinoic acid and 13-cis-retinoic acid are equally effective in inducing differentiation of HL-60. Retinol (vitamin A), retinal, and retinyl acetate are approximately 1/1000th less potent. This study suggests that retinoids could provide a therapeutic tool in the treatment of acute myeloid leukemia, a disease that has been looked upon as primarily involving a block in myeloid differentiation, and indicates that retinoids, in addition to their well-characterized involvement in epithelial cell differentiation, may also be involved in the differentiation of certain hematopoietic cells.
1,956 citations
TL;DR: The marked similarity in behavior of HL-60 cells and Friend cells in the presence of these inducing agents suggests that similar molecular mechanisms are involved in the induction of differentiation of these human myeloid and murine erythroid leukemic cells.
Abstract: A human leukemic cell line (designated HL-60) has recently been established from the peripheral blood leukocytes of a patient with acute promyelocytic leukemia. This cell line displays distinct morphological and histochemical commitment towards myeloid differentiation. The cultured cells are predominantly promyelocytes, but the addition of dimethyl sulfoxide to the culture induces them to differentiate into myelocytes, metamyelocytes, and banded and segmented neutrophils. All 150 clones developed from the HL-60 culture show similar morphological differentiation in the presence of dimethyl sulfoxide. Unlike the morphologically immature promyelocytes, the dimethyl sulfoxide-induced mature cells exhibit functional maturity as exemplified by phagocytic activity. A number of other compounds previously shown to induce erythroid differentiation of mouse erythroleukemia (Friend) cells can induce analogous maturation of the myeloid HL-60 cells. The marked similarity in behavior of HL-60 cells and Friend cells in the presence of these inducing agents suggests that similar molecular mechanisms are involved in the induction of differentiation of these human myeloid and murine erythroid leukemic cells.
1,556 citations
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TL;DR: By standardizing the technical conditions of the experiment it is possible to use this principle for the immunochemical determination of antigens, and the lower limit of the method was found to correspond to 0·0025 μg of antigen, and to an antigen concentrations of 1·25 μg per ml.
8,937 citations
TL;DR: An unsuspected abnormality in all cells from the nine patients with chronic myelogenous leukaemia has been detected with quinacrine fluorescence and various Giemsa staining techniques, suggesting that there may be a hitherto undetected translocation between the long arm of 22 and thelong arm of 9, producing the 9q+ chromosome.
Abstract: CELLS from nine consecutive patients with chronic myelogenous leukaemia (CML) have been analysed with quinacrine fluorescence and various Giemsa staining techniques. The Philadelphia (Ph1) chromosome in all nine patients represents a deletion of the long arm of chromosome 22 (22q−)1,2. An unsuspected abnormality in all cells from the nine patients has been detected with these new staining techniques. It consists of the addition of dully fluorescing material to the end of the long arm of one chromosome 9 (9q+). In Giemsa-stained preparations, this material appears as an additional faint terminal band in one chromosome 9. The amount of additional material is approximately equal to the amount missing from the Ph1 (22q−) chromosome, suggesting that there may be a hitherto undetected translocation between the long arm of 22 and the long arm of 9, producing the 9q+ chromosome.
4,103 citations
TL;DR: A combination of cytological and leukocyte culture techniques is described which constitutes a convenient, reliable approach for chromosome studies of humans and yields the following advantages: relative ease of obtaining blood and small volume required.
4,054 citations
TL;DR: The ACIF test was used as a tool to trace the Epstein‐Barr virus genome at the cellular level to study the complementfixing antigens of human lymphoblastoid cell lines.
Abstract: Anti-complement immunofluorescence (ACIF) was used to study the complementfixing antigens of human lymphoblastoid cell lines. These cell lines carry the Epstein-Barr virus (EBV) genome although only producer cultures synthetize EBV-specific antigens (virus capsid antigen, VCA and early antigen, EA) detectable by direct and indirect immunofluorescence, usually in less than 5% of the cells. The ACIF test revealed an antigen localized in the nucleus of the lymphoblastoid cells. In contrast to EA and VCA, this antigen was present in over 90% of the cells of both producer and non-producer cultures. The antigen was shown to be specific for EBV by comparing the reactions of 52 sera in the ACIF test. Sera giving the nuclear reaction contained antibodies to VCA, EA or antigens detectable by complement fixation tests on cell extracts, but sera without EBV antibodies failed to give the reaction. Weak, equivocal or discordant reactions occurred with six sera with low titres in VCA, EA or complement fixation tests. Cell lines derived by transformation of human and primate lymphocytes by EBV gave the nuclear reaction. Control cells with no known association with EBV were non-reactive. These included foetal lymphocytes transformed by phytohaemagglutinin, cell lines derived from breast cancer, glioma, normal glia, pleuritis maligna and myeloma, and two marmoset lymphoid lines carrying Herpesvirus saimiri (HVS). In preliminary experiments, the ACIF test was used as a tool to trace the EBV genome at the cellular level. Cells from two Burkitt lymphoma biopsies, one tested after biopsy and one after passaging in nude mice, contained an EBV-specific antigen. Three clones of cells derived from hybrids of mouse somatic cells and a human lymphoblastoid cell line also contained such an antigen, but the number of reactive cells varied from clone to clone. A fourth clone was non-reactive.
1,632 citations
1,399 citations