Use of All-trans Retinoic Acid in the Treatment of Acute Promyelocyte Leukemia

Meng-er, Huang; Ye, Yuchen; Chen, Shu-Rong; Jin-ren, Chai; Lü, Jin-Chun; Lin, Zhao; Longjun, GU; Wang, Zhenyi

doi:10.1007/978-3-642-74621-5_14

Cited by 22 publications

(27 citation statements)

References 22 publications

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“…Retinoids prevent the development of cancer of the skin and are effective as agents in the treatment of human premalignant and malignant cutaneous disorders (Lippman & Meyskens, 1989). In addition, retinoids are successfully used in the therapy of the acute promyelocytic leukaemia (Meng-er et al, 1988).Several intracellular proteins interacting with RA have been identified, such as the cellular retinoic acid binding protein (CRABP) and the nuclear retinoic acid receptors (RARs). Three RAR subtypes RAR-a, -P and -y have been identified so far (Petkovich et al, 1987;Giguere et al, 1987;Benbrook et al, 1988;Brand et al, 1988;Krust et al, 1989 NIH:OVCAR-3 and the ovarian teratocarcinoma cell line CRL 1572 (PA-1) were received from the American Tissue Type Culture Collection (ATCC, Rockville, MD, USA).…”

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Retinoic acid receptors in retinoid responsive ovarian cancer cell lines detected by polymerase chain reaction following reverse transcription

Harant¹,

Korschineck²,

Krupitza³

et al. 1993

Br J Cancer

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Summary The growth inhibitory effects of all-trans and 13-cis retinoic acid (RA) and of the synthetic retinoids TTNPB, TTNPB-ethylester and TTNN were studied on seven human epithelial ovarian cancer cell lines and one ovarian teratocarcinoma cell line. Six of seven ovarian adenocarcinoma cell lines were inhibited in their growth by RA and by synthetic retinoids in a dose dependent manner. No response to these substances was observed for the ovarian teratocarcinoma cell line. The knowledge that RA and retinoids exert their action on the cells via nuclear receptors led us to examine the expression of RAR-a, -,B and -mRNA by these cell lines by polymerase chain reaction following reverse transcription. All cell lines expressed RAR-x and -mRNA and six of the eight cell lines were found to express additionally RAR-P mRNA, among them the ovarian teratocarcinoma cell line. Our data indicate that there was no direct association between the presence of RAR subtype transcripts and the response to retinoids in ovarian cancer cell lines.Retinoic acid (RA) is a morphogenic compound involved in vertebrate development (Eichele, 1989) and it plays a major role in epithelial cell growth and cellular differentiation (Sporn et al., 1984). RA induces differentiation of mouse embryonal carcinoma cells in vitro and influences the development of the regenerating amphibian limb (for review see de Luca, 1991).It has also been shown that retinoids cause growth inhibition in many hyperproliferating cell lines, a feature that makes the compounds of fundamental interest as antitumour agents. Retinoids prevent the development of cancer of the skin and are effective as agents in the treatment of human premalignant and malignant cutaneous disorders (Lippman & Meyskens, 1989). In addition, retinoids are successfully used in the therapy of the acute promyelocytic leukaemia (Meng-er et al., 1988).Several intracellular proteins interacting with RA have been identified, such as the cellular retinoic acid binding protein (CRABP) and the nuclear retinoic acid receptors (RARs). Three RAR subtypes RAR-a, -P and -y have been identified so far (Petkovich et al., 1987;Giguere et al., 1987;Benbrook et al., 1988;Brand et al., 1988;Krust et al., 1989 NIH:OVCAR-3 and the ovarian teratocarcinoma cell line CRL 1572 (PA-1) were received from the American Tissue Type Culture Collection (ATCC, Rockville, MD, USA). All cell lines were cultivated in a-MEM (Gibco, Scotland) supplemented with 10% heat-inactivated foetal calf serum (Gibco, Scotland) and were maintained in an humidified 5% CO2 atmosphere at 37°C. Cultures were refed after 4 days and passaged weekly 1:5 -1:10.All cells were used within 30 passages from the original stock.Tests for mycoplasma contamination were negative (DAPI, Boehringer Mannheim, Germany). RetinoidsAll-trans RA, 1 3-cis RA, (E)-4- [2-(5,6,7,8-tetrahydro-5,5,8,8,-tetramethyl-2-naphthalenyl)-1-propenyl] benzoic acid -(5,6,7,8-tetrahydro-5,5,8,8,-tetramethyl-2-

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confidence: 99%

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confidence: 99%

Retinoic acid receptors in retinoid responsive ovarian cancer cell lines detected by polymerase chain reaction following reverse transcription

Harant¹,

Korschineck²,

Krupitza³

et al. 1993

Br J Cancer

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“…For example, RA induces terminal granulocytic differentiation of the HL-60 myeloid leukemia cell line (8) as well as certain fresh human AML cells in vitro (7). Moreover, as a single agent this compound induces complete remissions in certain patients with AML without inducing marrow aplasia (25,34) and thus is of potential therapeutic importance in certain leukemic disorders.…”

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Retinoic acid-induced granulocytic differentiation of HL-60 myeloid leukemia cells is mediated directly through the retinoic acid receptor (RAR-alpha).

Collins¹,

Robertson²,

Mueller³

1990

Mol. Cell. Biol.

306

127

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Retinoic acid (RA) induces terminal granulocytic differentiation of the HL-60 promyelocytic leukemia cell line as well as certain other human myeloid leukemias. Specific RA receptors that are members of the steroid-thyroid hormone superfamily of nuclear transcription factors have recently been identified. We developed an HL-60 subclone that was relatively resistant to RA-induced differentiation. Specific nuclear RA receptors in this RA-resistant subclone had a decreased affinity for RA and exhibited a lower molecular weight compared with nuclear RA receptors from the RA-sensitive parental HL-60 cells. Retroviral vector-mediated transduction of a single copy of the RA receptor (RAR-alpha) into this RA-resistant HL-60 subclone restored the sensitivity of these cells to RA. These observations indicate that RAR-alpha plays a critical and central role in mediating RA-induced terminal differentiation of HL-60 leukemia cells.

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“…The fusion protein joining RARa and myl, associated with increased cytotoxic response to ATRA in culture, provided an explanation for the remarkable clinical response to ATRA, with the disease often going into complete remission. 86,87 This early evidence was confirmed in large trials. While often APL patients treated with ATRA alone relapsed, the addition of an anthracycline drug to the regimen often resulted in long-term survival.…”

Section: Association Of Blast Characteristics With Choice Of Treatmenmentioning

confidence: 84%

Stem cells and diversity

McCulloch

2003

Leukemia

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Modern hematology began with two technology-based revolutions. First, assays were developed for cells earlier in lineages than those recognized morphologically. These opened for study important areas such as regulation and response to injury. Second, the rapid development of molecular biology disclosed complex mechanisms within cells and identified important genetic changes in malignancy. When immediate causative lesions were found, specific treatments directed at them were seen to be highly effective.Recently, several groups have provided evidence of the existence in adult tissues of stem cells that are capable of differentiation into such diverse organ systems as hematopoiesis, muscle, liver and brain. The implications of this stem cell plasticity are just beginning to be realized.The purpose of this paper is to review some of the concepts, advances and problems emerging from colony assays, molecular biology and stem cell plasticity. A hypothesis will be presented that links stem cell plasticity to the clinical entity known as metastases with unknown primary source. Colony assaysClonogenic assays, where a single cell gives rise to a recognizable colony, are selective, since they can measure minority populations; the assays are specific, quantitative, qualitative and provide information about the proliferative and differentiation capacities of the cells of origin. Each of these advantages of colony assays has limitations. The most severe limitation of the method is that analysis of cellular composition to determine progenitor properties shows only what the cell of origin did during clonal expansion, but not what it might do if conditions were improved or the time of observation prolonged.

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Use of All-trans Retinoic Acid in the Treatment of Acute Promyelocyte Leukemia

Cited by 22 publications

References 22 publications

Retinoic acid receptors in retinoid responsive ovarian cancer cell lines detected by polymerase chain reaction following reverse transcription

Retinoic acid receptors in retinoid responsive ovarian cancer cell lines detected by polymerase chain reaction following reverse transcription

Retinoic acid-induced granulocytic differentiation of HL-60 myeloid leukemia cells is mediated directly through the retinoic acid receptor (RAR-alpha).

Stem cells and diversity

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