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https://www.readbyqxmd.com/read/29021535/the-autophagy-scaffold-protein-alfy-is-critical-for-the-granulocytic-differentiation-of-aml-cells
#1
Anna M Schläfli, Pauline Isakson, E Garattini, Anne Simonsen, Mario P Tschan
Acute myeloid leukemia (AML) is a malignancy of myeloid progenitor cells that are blocked in differentiation. Acute promyelocytic leukemia (APL) is a rare form of AML, which generally presents with a t(15;17) translocation causing expression of the fusion protein PML-RARA. Pharmacological doses of all-trans retinoic acid (ATRA) induce granulocytic differentiation of APL cells leading to cure rates of >80% if combined with conventional chemotherapy. Autophagy is a lysosomal degradation pathway for the removal of cytoplasmic content and recycling of macromolecules...
October 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28984423/the-triple-negative-cd34-hla-dr-cd11b-profile-rapidly-and-specifically-identifies-an-acute-promyelocytic-leukemia
#2
K Rahman, R Gupta, M K Singh, M K Sarkar, A Gupta, S Nityanand
INTRODUCTION: The genetic testing to confirm or rule out an acute promyelocytic leukemia (APL) typically takes a minimum of 24-72 hours. Flow cytometric immunophenotyping (FCI) on the other hand provides rapid and objective information to differentiate APL from non-APL. METHODS: FCI features, with single-tube 8-color combination using CD45, CD34, HAL-DR, CD11b, CD13, CD33, and CD117 and CD64, were compared for the 30 consecutive APL and 30 non-APL acute myeloid leukemia (AML) cases which morphologically mimicked an APL...
October 6, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28794865/recent-advances-in-acute-promyelocytic-leukaemia
#3
REVIEW
Chin-Hin Ng, Wee-Joo Chng
Acute promyelocytic leukaemia (APML) is a subtype of leukaemia arising from a distinct reciprocal translocation involving chromosomes 15 and 17, which results in the PML-RARA fusion gene. Over the past three decades, APML has been transformed from a highly fatal disease to a highly curable one. This drastic improvement is because of the introduction of a new treatment strategy with all-trans retinoic acid and, more recently, arsenic trioxide. The revolutionary treatment of APML has also paved the way for a new cancer treatment, which is genetically targeted therapy...
2017: F1000Research
https://www.readbyqxmd.com/read/28767575/dnmt3a-mutations-in-chinese-childhood-acute-myeloid-leukemia
#4
Weijing Li, Lei Cui, Chao Gao, Shuguang Liu, Xiaoxi Zhao, Ruidong Zhang, Huyong Zheng, Minyuan Wu, Zhigang Li
BACKGROUND: DNA methyltransferase 3A (DNMT3A) mutations have been found in approximately 20% of adult acute myeloid leukemia (AML) patients and in 0% to 1.4% of children with AML, and the hotspots of mutations are mainly located in the catalytic methyltransferase domain, hereinto, mutation R882 accounts for 60%. Although the negative effect of DNMT3A on treatment outcome is well known, the prognostic significance of other DNMT3A mutations in AML is still unclear. Here, we tried to determine the incidence and prognostic significance of DNMT3A mutations in a large cohort in Chinese childhood AML...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28735486/detection-and-quantification-of-acute-myeloid-leukemia-associated-fusion-transcripts
#5
Jonathan Schumacher, Philippe Szankasi, Todd W Kelley
Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR)-based detection of abnormal fusion transcripts is an important strategy for the diagnosis and monitoring of patients with acute myeloid leukemia (AML) with t(8;21)(q22;q22); RUNX1-RUNX1T1, inv(16)(p13.1;q22); CBFB-MYH11 or t(15;17)(q22;q12); PML-RARA. In RT-qPCR assays, patient-derived cDNA is subjected to amplification using PCR primers directed against the fusion transcript of interest as well as a reference gene for normalization...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28599418/acute-promyelocytic-leukemia-with-a-cryptic-insertion-of-rara-into-pml-on-chromosome-15-due-to-uniparental-isodisomy-a-case-report
#6
Anna Venci, Rita Mazza, Orietta Spinelli, Luciana Di Schiena, Daniela Bettio
Acute promyelocytic leukemia is a myeloid disorder that is characterized by the specific t(15;17) variant in ~98% of cases. The typical hypergranular and microgranular or hypogranular types exist, and are frequently associated with disseminated intravascular coagulopathy. Rare cases of promyelocytic leukemia-retinoic acid receptor α (PML-RARA) fusion without the reciprocal RARA-PML have been reported in cytogenetically normal samples. Conversely, fluorescence in situ hybridization (FISH) analysis has revealed a cryptic insertion of the RARA gene into the PML gene on chromosome 15...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28567073/quantitative-assessment-of-wilms-tumor-1-expression-by-real-time-quantitative-polymerase-chain-reaction-in-patients-with-acute-myeloblastic-leukemia
#7
Hossein Ayatollahi, Mohammad Hadi Sadeghian, Mahmood Naderi, Amir Hossein Jafarian, Seyyede Fatemeh Shams, Neda Motamedirad, Maryam Sheikhi, Afsane Bahrami, Sepideh Shakeri
BACKGROUND: The Wilms tumor 1 (WT1) gene is originally defined as a tumor suppressor gene and a transcription factor that overexpressed in leukemic cells. It is highly expressed in more than 80% of acute myeloid leukemia (AML) patients, both in bone marrow (BM) and in peripheral blood (PB), and it is used as a powerful and independent marker of minimal residual disease (MRD); we have determined the expression levels of the WT1 by real-time quantitative polymerase chain reaction (RQ-PCR) in PB and BM in 126 newly diagnosed AML patients...
2017: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/28540746/kdm3b-shows-tumor-suppressive-activity-and-transcriptionally-regulates-hoxa1-through-retinoic-acid-response-elements-in-acute-myeloid-leukemia
#8
Xin Xu, Stefan Nagel, Hilmar Quentmeier, Zhanju Wang, Claudia Pommerenke, Wilhelm G Dirks, Roderick A F Macleod, Hans G Drexler, Zhenbo Hu
KDM3B reportedly shows both tumor-suppressive and tumor-promoting activities in leukemia. The function of KDM3B is likely cell-type dependent and its seeming functional discordance may reflect its phenotypic dependence on downstream targets. Here, we first showed the underexpression of KDM3B in acute myeloid leukemia (AML) patients and AML cell lines with MLL-AF6/9 or PML-RARA translocations. Overexpression of KDM3B repressed colony formation of AML cell line with 5q deletion. We then performed global microarray profiling to identify potential downstream targets of KDM3B, notably HOXA1, which was verified by real time PCR and Western blotting...
May 25, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28511493/isolated-central-nervous-system-cns-relapse-in-paediatric-acute-promyelocytic-leukaemia-a-systematic-review
#9
REVIEW
Smeeta Gajendra, Rashmi Ranjan Das, Rashi Sharma
INTRODUCTION: Extramedullary disease, as a whole, is rare in Acute Promyelocytic Leukaemia (APML). If at all relapse occurs, following sites are involved: Central Nervous System (CNS), skin, testes, mediastinum, gingiva, and ear. Isolated CNS relapses after complete morphological and molecular remission is rarer particularly in children. AIM: To review the literature systematically to find out the incidence of isolated CNS relapse in paediatric APML cases. MATERIALS AND METHODS: A systematic search of major databases (Medline, Pubmed and Google Scholar) was conducted...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28496950/development-of-flow-cytometry-fluorescent-in-situ-hybridization-flow-fish-method-for-detection-of-pml-rara-chromosomal-translocation-in-acute-promyelocytic-leukemia-cell-line
#10
Fatemeh Zahedipour, Reza Ranjbaran, Abbas Behzad Behbahani, Khalil Tavakol Afshari, Mohammad Ali Okhovat, Gholamhossein Tamadon, Sedigheh Sharifzadeh
BACKGROUND: Acute Promyelocytic Leukemia (APL) is a subclass of acute myeloid leukemia. The chromosomal aberration in 95% of APL cases is t(15; 17) (q22; q21), which prevents cell differentiation. Characterization of the underlying molecular lesion is valuable in determining optimal treatment strategy. The goal of this study was to develop a new and powerful Flow- FISH technique to detect the long isoform (L) of PML-RARa fusion transcript in NB4 cell line. METHODS: To achieve the best condition for fixation, two different fixatives including 2% paraformaldehyde and 75% ethanol were used...
April 2017: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/28427227/high-dose-ascorbate-and-arsenic-trioxide-selectively-kill-acute-myeloid-leukemia-and-acute-promyelocytic-leukemia-blasts-in-vitro
#11
Nélida I Noguera, Elvira Pelosi, Daniela F Angelini, Maria Liliana Piredda, Gisella Guerrera, Eleonora Piras, Luca Battistini, Lauretta Massai, Anna Berardi, Gianfranco Catalano, Laura Cicconi, Germana Castelli, Agnese D'Angiò, Luca Pasquini, Grazia Graziani, Giuseppe Fioritoni, Maria Teresa Voso, Domenico Mastrangelo, Ugo Testa, Francesco Lo-Coco
The use of high-dose ascorbate (ASC) for the treatment of human cancer has been attempted several decades ago and has been recently revived by several in vitro and in vivo studies in solid tumors. We tested the cytotoxic effects of ASC, alone or in combination with arsenic trioxide (ATO) in acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL). Leukemic cell lines and primary blasts from AML and APL patients were treated with graded concentrations of ASC, alone or in association with standard concentration (1 μM) of ATO...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411256/epigenetically-induced-ectopic-expression-of-uncx-impairs-the-proliferation-and-differentiation-of-myeloid-cells
#12
Giulia Daniele, Giorgia Simonetti, Caterina Fusilli, Ilaria Iacobucci, Angelo Lonoce, Antonio Palazzo, Mariana Lomiento, Fabiana Mammoli, Renè Massimiliano Marsano, Elena Marasco, Vilma Mantovani, Hilmar Quentmeier, Hans G Drexler, Jie Ding, Orazio Palumbo, Massimo Carella, Niroshan Nadarajah, Margherita Perricone, Emanuela Ottaviani, Carmen Baldazzi, Nicoletta Testoni, Cristina Papayannidis, Sergio Ferrari, Tommaso Mazza, Giovanni Martinelli, Clelia Tiziana Storlazzi
We here describe a leukemogenic role of the homeobox gene UNCX, activated by epigenetic modifications in acute myeloid leukemia (AML). We found the ectopic activation of UNCX in a leukemia patient harboring a t(7;10)(p22;p14) translocation, in 22 of 61 of additional cases [a total of 23 positive patients out of 62 (37.1%)], and in 6 of 75 (8%) of AML cell lines. UNCX is embedded within a low-methylation region (canyon) and encodes for a transcription factor involved in somitogenesis and neurogenesis, with specific expression in the eye, brain, and kidney...
July 2017: Haematologica
https://www.readbyqxmd.com/read/28352191/retinoic-acid-and-arsenic-trioxide-in-the-treatment-of-acute-promyelocytic-leukemia-current-perspectives
#13
REVIEW
Derek McCulloch, Christina Brown, Harry Iland
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) with a unique morphological appearance, associated coagulopathy and canonical balanced translocation of genetic material between chromosomes 15 and 17. APL was first described as a distinct subtype of AML in 1957 by Dr Leif Hillestad who recognized the pattern of an acute leukemia associated with fibrinolysis, hypofibrinogenemia and catastrophic hemorrhage. In the intervening years, the characteristic morphology of APL has been described fully with both classical hypergranular and variant microgranular forms...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28268092/droplet-digital-pcr-is-a-reliable-tool-for-monitoring-minimal-residual-disease-in-acute-promyelocytic-leukemia
#14
Claudia Brunetti, Luisa Anelli, Antonella Zagaria, Angela Minervini, Crescenzio F Minervini, Paola Casieri, Nicoletta Coccaro, Cosimo Cumbo, Giuseppina Tota, Luciana Impera, Paola Orsini, Giorgina Specchia, Francesco Albano
Nested RT-PCR (nPCR) and real-time quantitative PCR (qPCR) are well-established methods for monitoring minimal residual disease (MRD) in acute promyelocytic leukemia (APL). Despite their remarkable sensitivity and specificity, both methods have inherent limitations, such as qualitative MRD evaluation and relative quantification. Herein, we used droplet digital PCR (ddPCR) to monitor MRD in 21 APL patients and compared its performance with nPCR and qPCR. After assessing the limit of detection (LOD) for each technique on serial dilutions of PML-RARA bcr1 and bcr3 transcripts, a total of 48 follow-up samples were analyzed and the results compared...
May 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28238096/clinical-impact-of-galectin-3-in-newly-diagnosed-t-15-17-q22-q21-pml-rara-acute-promyelocytic-leukemia-treated-with-all-trans-retinoic-acid-and-arsenic-trioxide-based-regimens
#15
Na Gao, Xue-Xia Wang, Jian-Rong Sun, Wen-Zheng Yu, Xi-Zhi Li
Increased galectin-3 expression has been currently showed to be associated with poor prognosis in some hematological malignancies, such as acute myeloid leukemia, diffuse large B cell lymphoma. However, little is known about the clinical significance of galectin-3 in patients with acute promyelocytic leukemia (APL). We investigated the concentration of serum galectin-3 and characterized the relationship between galectin-3 and outcome in patients with APL. Higher galectin-3 levels were detected in patients with APL compared with the healthy controls (p < 0...
May 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28183680/diagnosis-of-variant-rara-translocation-using-standard-dual-color-dual-fusion-pml-rara-fish-probes-an-illustrative-report
#16
Manish Kumar Singh, Mayur Parihar, Neeraj Arora, Deepak Kumar Mishra, Saurabh Jayant Bhave, Mammen Chandy
Acute promyelocytic leukemia (APML) with variant RARa translocations comprises 1-2% of APML cases. However, the diagnosis of these cases is challenging as the routine practice includes fluorescence in situ hybridization (FISH) reverse transcription polymerase chain reaction targeting the PML and RARA genes to detect PML/RARA fusions. Here, we report a case highlighting the importance of atypical FISH signal patterns in standard dual-color dual-fusion PML/RARa FISH analysis complimented by karyotyping to detect these variant RARA translocations...
February 1, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28101221/a-complex-translocation-3-17-15-in-acute-promyelocytic-leukemia-confirmed-by-fluorescence-in-situ-hybridization
#17
Yanming Wang, Junjie Ma, Xinguang Liu, Riming Liu, Lingling Xu, Li Wang, Jiannong Cen, Xiaoxia Chu
Acute promyelocytic leukemia (APL) is typified by t(15;17)(q22;q21), generating the promyelocytic leukemia (PML) gene at 15q22 with the retinoic acid α-receptor (RARA) gene at 17q21. The PML-RARA fusion gene is believed to play a vital role in leukemogenesis. A sizeable minority of patients with complex variants of APL have been reported. The present study reports the case of a 33-year-old male with APL carrying a potential complex translocation. The initial symptom was bleeding gums. Chromosomal analysis of the bone marrow cells revealed an atypical 17q aberration...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28035072/%C3%AE-np73-overexpression-promotes-resistance-to-apoptosis-but-does-not-cooperate-with-pml-rara-in-the-induction-of-an-apl-leukemic-phenotype
#18
Antonio R Lucena-Araujo, Juan L Coelho-Silva, Diego A Pereira-Martins, Carolina Thomé, Priscila S Scheucher, Ana P Lange, Helder H Paiva, Benjamin T Hemmelgarn, Mariana C Morais-Sobral, Elisa A Azevedo, Pedro L Franca-Neto, Rafael F Franca, Cleide L Silva, Alexandre Krause, Eduardo M Rego
Here, we evaluated whether the overexpression of transcriptionally inactive ΔNp73 cooperates with PML/RARA fusion protein in the induction of an APL-leukemic phenotype, as well as its role in vitro in proliferation, myeloid differentiation, and drug-induced apoptosis. Using lentiviral gene transfer, we showed in vitro that ΔNp73 overexpression resulted in increased proliferation in murine bone marrow (BM) cells from hCG-PML/RARA transgenic mice and their wild-type (WT) counterpart, with no accumulation of cells at G2/M or S phases; instead, ΔNp73-expressing cells had a lower rate of induced apoptosis...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28030795/aml-associated-oncofusion-proteins-pml-rara-aml1-eto-and-cbfb-myh11-target-runx-ets-factor-binding-sites-to-modulate-h3ac-levels-and-drive-leukemogenesis
#19
Abhishek A Singh, Amit Mandoli, Koen H M Prange, Marko Laakso, Joost H A Martens
Chromosomal translocations are one of the hallmarks of acute myeloid leukemia (AML), often leading to gene fusions and expression of an oncofusion protein. Over recent years it has become clear that most of the AML associated oncofusion proteins molecularly adopt distinct mechanisms for inducing leukemogenesis. Still these unique molecular properties of the chimeric proteins converge and give rise to a common pathogenic molecular mechanism. In the present study we compared genome-wide DNA binding and transcriptome data associated with AML1-ETO, CBFB-MYH11 and PML-RARA oncofusion protein expression to identify unique and common features...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28028303/dismal-outcome-of-therapy-related-myeloid-neoplasm-associated-with-complex-aberrant-karyotypes-and-monosomal-karyotype-a-case-report
#20
Y L Tang, W K Chia, E C S W Yap, M I Julia, C F Leong, S Salwati, C L Wong
INTRODUCTION: Individuals who are exposed to cytotoxic agents are at risk of developing therapyrelated myeloid neoplasms (t-MN). Cytogenetic findings of a neoplasm play an important role in stratifying patients into different risk groups and thus predict the response to treatment and overall survival. CASE REPORT: A 59-year-old man was diagnosed with acute promyelocytic leukaemia. Following this, he underwent all-trans retinoic acid (ATRA) based chemotherapy and achieved remission...
December 2016: Malaysian Journal of Pathology
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