Analysis of telomerase activity and RNA expression in a patient with acute promyelocytic leukemia treated with all‐<i>trans</i> retinoic acid

Akiyama, Masaharu; Yanagisawa, Takaaki; Fujisawa, Kohji; Eto, Yoshikatsu

doi:10.1002/pbc.20392

Cited by 7 publications

(5 citation statements)

References 21 publications

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“…All‐ trans retinoic acid may also exert its effects via a non‐receptor pathway by activating nuclear factors, such as C/EBP 11–16 . Because the JWA proximal promoter region does not contain RARE but does contains two CCAAT boxes, which C/EBP may bind to, the expression of JWA may be mediated by ATRA‐ activated C/EBP, which binds to CCAAT boxes of the JWA promoter, and this may critical for the antiproliferation and pro‐apoptosis role of ATRA; however, direct evidence of this needs to be provided.…”

Section: Discussionmentioning

confidence: 99%

“…The RAR and RXR modulate the expression of target genes by interacting as either homodimers or heterodimers with the retinoic acid response element (RARE) located in the promoter regions of target genes 10 . Furthermore, ATRA may also exert its effects via a non‐receptor pathway by activating nuclear factors, such as the CCAAT/enhancer binding proteins (C/EBP) 11–14 . It had been shown that C/EBPα is involved in the activation of Hp gene expression by ATRA in human monocytic cells 15 .…”

Section: Introductionmentioning

confidence: 99%

“…10 Furthermore, ATRA may also exert its effects via a non-receptor pathway by activating nuclear factors, such as the CCAAT/enhancer binding proteins (C/EBP). [11][12][13][14] It had been shown that C/EBPa is involved in the activation of Hp gene expression by ATRA in human monocytic cells. 15 The coactivator activating signal cointegrator-2 (ASC-2) plays an important role in the differentiation of HL-60 cells into granulocytes by mediating C/EBPa-induced gene transcription.…”

Section: Introductionmentioning

confidence: 99%

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JWA IS REQUIRED FOR THE ANTIPROLIFERATIVE AND PRO‐APOPTOTIC EFFECTS OF ALL‐TRANS RETINOIC ACID IN HELA CELLS

Mao

Liu

Chen

et al. 2006

Clin Exp Pharma Physio

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1. All-trans retinoic acid (ATRA) is known to inhibit cellular proliferation and induce differentiation and apoptosis. It usually activates gene expression by binding to a nuclear receptor that interacts with retinoic acid-response elements (RARE) and then activates the mitogen-activated protein kinase signal pathway. JWA, a newly identified ATRA-responsive gene, has recently been proposed as an important molecule for cellular differentiation induced by some chemicals, including ATRA. 2. To investigate the possible involvement of JWA in the inhibition of cellular proliferation and induction of apoptosis by ATRA, HeLa cells were stably transfected with sense or antisense JWA to establish cell lines that overexpressed or were deficient in JWA; ATRA (0.05-10 micromol/L) was used to induce cellular differentiation and apoptosis. 3. Western blot analysis revealed that ATRA caused increased expression of JWA in HeLa cells in a dose- and time-dependent manner, accompanied by activation of extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. However, ERK1/2 phosphorylation induced by ATRA was inhibited in JWA-deficient HeLa cells. In JWA-overexpressing HeLa cells, ATRA showed more significant antiproliferative effects and induced more apoptosis. 4. The reporter gene assay showed that ATRA (5 mmol/L) enhanced the transcriptional activity of JWA by interacting with its promoter in the region from -194 to +107 bp (P < 0.01). Bioinformatic analysis indicated that the JWA promoter did not contain RARE, but did contain two CCAAT boxes in this fragment spanning -194 to +107 bp, which may be responsive to the ATRA-activated nuclear transcription factor CCAAT/enhancer binding proteins (C/EBP) or interacting proteins. Therefore, ATRA-inhibited cellular proliferation and -induced apoptosis in HeLa cells may be dependent on JWA transactivation via its C/EBP-binding motifs. 5. These data indicate that the inhibition of proliferation and the induction of apoptosis by ATRA are dependent on JWA expression in HeLa cells. The findings may represent a novel mechanism by which the effects of ATRA in regulating cellular proliferation and apoptosis are mediated, at least in part, by JWA expression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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JWA IS REQUIRED FOR THE ANTIPROLIFERATIVE AND PRO‐APOPTOTIC EFFECTS OF ALL‐TRANS RETINOIC ACID IN HELA CELLS

Mao

Liu

Chen

et al. 2006

Clin Exp Pharma Physio

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“…It is clear that the terminal maturation of tumor cells is associated with the repression of telomerase activity [14,15], which has also been confirmed in leukemia [25,26]. In APL, ATRA treatment leads to a rapid decrease in telomerase activity both in the primary cell and the cell line with two pathways, the RAR3-dependent and RXR3-dependent pathways [27,28], and we further found that it was TANK1, not TANK2, that positively regulates telomerase activity, and that Pinx1 expression may also be involved [29]. In this study, we found that the relative telomerase activity of NB4-LR1 cells was significantly higher than that of NB4 cells, and the treatment of ATRA can reduce the level as remarkably as in NB4 cells.…”

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confidence: 80%

Matrine Cooperates with All-Trans Retinoic Acid on Differentiation Induction of All-Trans Retinoic Acid-Resistant Acute Promyelocytic Leukemia Cells (NB4-LR1): Possible Mechanisms

Shao

Sun

et al. 2014

Planta Med

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Retinoic acid resistance results in refractory disease, and recovery in acute promyelocytic leukemia remains a challenge in clinical practice, with no ideal chemotherapeutic drug currently available. Here we report on the effect of an active compound of Sophora flavescens called matrine (0.1 mmol/L) combined with all-trans retinoic acid (1 µmol/L) in alleviating retinoic acid resistance in acute promyelocytic leukemia-derived NB4-LR1 cells by differentiation induction, as can be seen by an induced morphology change, increased CD11b expression, and nitro blue tetrazolium reduction activity, and a decreased expression of the promyelocytic leukemia-retinoic acid receptor α fusion gene and protein product. We further explored the probable mechanism of how matrine promotes the recovery of differentiation ability in NB4-LR1 cells when exposed to all-trans retinoic acid. We observed that the combination of all-trans retinoic acid and matrine can increase the level of cyclic adenosine monophosphate and protein kinase A activity, reduce telomerase activity, and downregulate the protein expression of topoisomerase II beta in NB4-LR1 cells. The results of this study suggest the possible clinical utility of matrine in the treatment of retinoic acid-resistant acute promyelocytic leukemia.

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“…Although the A 260 /A 280 ratios of the RNA in FFOE BM was 1.71 ± 0.06, which is slightly lower than that of fresh BM, the RNA quality was good enough to obtain 28s and 18s rRNA bands and enabled RT-PCR for BCR-ABL fusion transcript to be performed. Well-preserved DNA and RNA is critically important for the research of haematological malignancies (Florell et al, 2001;Thö rn et al, 2005;Akiyama et al, 2006), because mutations or over-expressions of specific genes may be of diagnostic (Kang et al, 2002) or prognostic importance (Shanafelt, Geyer & Kay, 2004;Tallman, Gilliland & Rowe, 2005).…”

Section: Discussionmentioning

confidence: 99%

Fresh‐frozen, optimal cutting temperature (OCT) compound‐embedded bone marrow aspirates: a reliable resource for morphological, immunohistochemical and molecular examinations

Lim¹,

Kim²,

Lee³

et al. 2010

Int J Lab Hematology

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The usefulness of fresh-frozen, optimal cutting temperature (OCT) compound-embedded (FFOE) bone marrow (BM) aspirates was evaluated as a reliable resource for morphological, immunohistochemical and molecular examinations. One hundred BM aspirates were collected in polypropylene tubes and immediately frozen for 2 h in a deep freezer. Frozen BM was transferred to a cryomold filled with OCT compound and the prepared samples were stored in a deep freezer. Histological examination and immunohistochemical staining, polymerase chain reaction (PCR), sequencing and reverse transcription (RT)-PCR were performed to evaluate the quality of the FFOE BM sections in 10% of randomly selected samples. FFOE BM sections revealed better morphologies than paraffin-embedded clot sections in haematoxylin and eosin staining because mature erythrocytes were removed during the staining process in frozen BM sections. Immunohistochemical staining for CD34 revealed excellent staining quality and oil red O staining showed that fat vacuoles in cells were well preserved. The quality of genomic DNA in FFOE BM sections was suitable for obtaining about 2000 bp PCR product for the human leucocyte antigen-A locus followed by direct sequencing of the sample, and the quality of total RNA was suitable for detection of BCR-ABL fusion transcript. FFOE BM aspirates are a reliable resource for various laboratory tests of diagnostic and research arenas.

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Analysis of telomerase activity and RNA expression in a patient with acute promyelocytic leukemia treated with all‐trans retinoic acid

Cited by 7 publications

References 21 publications

JWA IS REQUIRED FOR THE ANTIPROLIFERATIVE AND PRO‐APOPTOTIC EFFECTS OF ALL‐TRANS RETINOIC ACID IN HELA CELLS

JWA IS REQUIRED FOR THE ANTIPROLIFERATIVE AND PRO‐APOPTOTIC EFFECTS OF ALL‐TRANS RETINOIC ACID IN HELA CELLS

Matrine Cooperates with All-Trans Retinoic Acid on Differentiation Induction of All-Trans Retinoic Acid-Resistant Acute Promyelocytic Leukemia Cells (NB4-LR1): Possible Mechanisms

Fresh‐frozen, optimal cutting temperature (OCT) compound‐embedded bone marrow aspirates: a reliable resource for morphological, immunohistochemical and molecular examinations

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