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https://www.readbyqxmd.com/read/29237593/identification-of-novel-recurrent-stat3-rara-fusions-in-acute-promyelocytic-leukemia-lacking-t-15-17-q22-q12-pml-rara
#1
Li Yao, Lijun Wen, Nana Wang, Tianhui Liu, Yang Xu, Changgeng Ruan, Depei Wu, Suning Chen
No abstract text is available yet for this article.
December 13, 2017: Blood
https://www.readbyqxmd.com/read/29200671/multiplex-approach-in-classification-diagnosis-and-prognostication-in-acute-myeloid-leukemia-an-experience-from-tertiary-cancer-center-in-south-india
#2
Rachna Khera, Faiq Ahmed, Manasi Chetan Mundada, Sandhya G Devi, Sudha S Murthy, Nambaru Lavanya, Senthil J Rajappa, Krishna Mohan Mallavarapu, A Santa
Introduction: Acute myeloid leukemia (AML) is a heterogeneous group of disorders classified as per FAB subtypes and more recently by WHO by underlying genetic abnormalities. Aims and Objectives: This study aims to analyze the morphology, immunophenotype, cytogenetic and molecular abnormalities in around 200 patients of AML diagnosed over a period of 7 years at our institute and to determine relative frequency of various subtypes (based on FAB and WHO classification)...
July 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29137406/the-forkhead-box-c1-foxc1-transcription-factor-is-downregulated-in-acute-promyelocytic-leukemia
#3
Emiliano Fabiani, Giulia Falconi, Nélida Inés Noguera, Ernestina Saulle, Laura Cicconi, Mariadomenica Divona, Cristina Banella, Alessandra Picardi, Anna Maria Cerio, Letizia Boe, Massimo Sanchez, Elvira Pelosi, Ugo Testa, Francesco Lo-Coco, Maria Teresa Voso
Forkhead box (FOX) genes encode transcription factors, which regulate embryogenesis and play an important role in hematopoietic differentiation and in mesenchymal niche maintenance. Overexpression of the family member FOXC1 has been reported in solid tumors and acute myeloid leukemia (AML). We studied FOXC1 expression and function in acute promyelocytic leukemia (APL) and normal hematopoietic progenitors. FOXC1 mRNA and protein levels were significantly lower in primary marrow samples from 27 APL patients, as compared to samples obtained from 27 patients with other AML subtypes, and 5 normal CD34+ hematopoietic cells...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136503/acute-promyelocytic-leukemia-a-paradigm-for-oncoprotein-targeted-cure
#4
REVIEW
Hugues de Thé, Pier Paolo Pandolfi, Zhu Chen
Recent clinical trials have demonstrated that the immense majority of acute promyelocytic leukemia (APL) patients can be definitively cured by the combination of two targeted therapies: retinoic acid (RA) and arsenic. Mouse models have provided unexpected insights into the mechanisms involved. Restoration of PML nuclear bodies upon RA- and/or arsenic-initiated PML/RARA degradation is essential, while RA-triggered transcriptional activation is dispensable for APL eradication. Mutations of the arsenic-binding site of PML/RARA, but also PML, have been detected in therapy-resistant patients, demonstrating the key role of PML in APL cure...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29114972/frontline-therapy-of-acute-promyelocytic-leukemia-randomized-comparison-of-atra-and-intensified-chemotherapy-versus-atra-and-anthracyclines
#5
Eva Lengfelder, Dennis Görlich, Daniel Nowak, Karsten Spiekermann, Claudia Haferlach, Utz Krug, Karl-Anton Kreuzer, Jan Braess, Christoph Schliemann, Hans-Walter Lindemann, Heinz A Horst, Xaver Schiel, Michael Flasshove, Anna Hecht, Susanne Schnittger, Stephanie Schneider, Bernhard Wörmann, Wolf-Karsten Hofmann, Wolfgang E Berdel, Eike Bormann, Cristina Sauerland, Thomas Büchner, Wolfgang Hiddemann
OBJECTIVES: Randomized comparison of two treatment strategies in frontline therapy of acute promyelocytic leukemia (APL): all-trans retinoic acid (ATRA) and double induction intensified by high dose cytosine arabinoside (HD ara-C) (German AMLCG) and therapy with ATRA and anthracyclines (Spanish PETHEMA, LPA99). PATIENTS AND RESULTS: Eighty of 87 adult patients with genetically confirmed APL of all risk groups were eligible. The outcome of both arms was similar: AMLCG vs PETHEMA: hematological complete remission 87% vs 83%, early death 13% vs 17% (p=0...
November 7, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29105243/performance-of-multiplex-fusion-gene-testing-in-pediatric-acute-myeloid-leukemia
#6
Yuka Iijima-Yamashita, Hidemasa Matsuo, Miho Yamada, Takao Deguchi, Nobutaka Kiyokawa, Akira Shimada, Akio Tawa, Hiroyuki Takahashi, Daisuke Tomizawa, Takashi Taga, Akitoshi Kinoshita, Souichi Adachi, Keizo Horibe
BACKGROUND: Gene abnormalities, particularly chromosome rearrangements generating gene fusions, are associated with clinical characteristics and prognosis in pediatric acute myeloid leukemia (AML). Karyotyping is generally performed to enable risk stratification; however, the results are not always consistent with those generated by reverse transcription-polymerase chain reaction (RT-PCR), and more accurate and rapid methods are required. METHODS: A total of 487 samples from de novo AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 study (n = 448), and acute promyelocytic leukemia (APL) patients enrolled in the JPLSG AML-P05 study (n = 39) were available for this investigation...
November 4, 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/29081694/recurrent-fusion-genes-in-leukemia-an-attractive-target-for-diagnosis-and-treatment
#7
REVIEW
Yuhui Wang, Nan Wu, Duo Liu, Yan Jin
INTRODUCTION: Since the first fusion gene was discovered decades ago, a considerable number of fusion genes have been detected in leukemia. The majority of them are generated through chromosomal rearrangement or abnormal transcription. With the development of techniques, high-throughput sequencing method makes it possible to detect fusion genes systematically in multiple human cancers. Owing to their biological significance and tumor-specific expression, some of the fusion genes are attractive diagnostic tools and therapeutic targets...
October 2017: Current Genomics
https://www.readbyqxmd.com/read/29021535/the-autophagy-scaffold-protein-alfy-is-critical-for-the-granulocytic-differentiation-of-aml-cells
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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