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https://www.readbyqxmd.com/read/28183680/diagnosis-of-variant-rara-translocation-using-standard-dual-color-dual-fusion-pml-rara-fish-probes-an-illustrative-report
#1
Manish K Singh, Mayur Parihar, Neeraj Arora, D K Mishra, Saurabh J 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
#2
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
#3
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
#4
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...
December 24, 2016: 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
#5
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
https://www.readbyqxmd.com/read/28028302/acute-promyelocytic-leukaemia-with-a-novel-translocation-t-16-17-q12-p13-a-case-report
#6
H Bhat, S Geelani, M Rashid, T Bhat, M Qadri, N Bashir N, F Manzoor, S Bhat, F Rather, J Rasool
Acute promyelocytic leukaemia (APML) is characterised by the t(15;17)(q22;q21), that results in the fusion of the promyelocytic leukaemia (PML) gene at 15q22 with the retinoic acid α-receptor (RARA) gene at 17q21. The current case report describes a 13-year-old male with APML, who was negative for PML/RARA fusion signal but reported to have an atypical translocation t(16;17). To the best of our knowledge this is the first case report of APML responsive to ATRA with such a translocation.
December 2016: Malaysian Journal of Pathology
https://www.readbyqxmd.com/read/28025581/pml-rara-associated-cooperating-mutations-belong-to-a-transcriptional-network-that-is-deregulated-in-myeloid-leukemias
#7
C Ronchini, A Brozzi, L Riva, L Luzi, A M Gruszka, G E M Melloni, E Scanziani, G Dharmalingam, M Mutarelli, V Belcastro, S Lavorgna, V Rossi, O Spinelli, A Biondi, A Rambaldi, F Lo-Coco, D di Bernardo, P G Pelicci
It has been shown that individual Acute Myeloid Leukemia (AML) patients are characterized by one of few initiating DNA mutations and 5-10 cooperating mutations not yet defined among hundreds identified by massive sequencing of AML genomes. We report an in vivo insertional mutagenesis screen for genes cooperating with one AML initiating mutations (PML-RARA, oncogene of acute promyelocytic leukemia, APL), which allowed identification of hundreds of genetic cooperators. The cooperators are mutated at low frequency in APL or AML patients but are always abnormally expressed in a cohort of 182 APLs and AMLs analyzed...
December 27, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28024467/-features-of-immunophenotypes-and-characteristics-of-molecular-biology-and-cellular-genetics-of-aml-patients-with-cd4-and-cd7-expression
#8
Tie-Qiang Liu, Shan Huang, Bo Yao, Zhi-Qing Liu, Chang-Lin Yu, Jian-Hui Qiao, Qi-Yun Sun, Kai-Xun Hu, Ya-Jing Huang, Rui Zhang, Yu-Fang Li, Juan Bai, Yu-Jing Sun, Bing-Xia Li, Dong-Mei Wang, Yi Wang, Mei Guo
OBJECTIVE: To explore the features of immunophenotypes and the characteristics of molecular biology and cellular genetics of AML patients with CD7 and CD4 expression. METHODS: The immunophenotypical markers of AML cells were detected by multiple parameter flow cytometry; the expression of WT1, MDK, ETO, PML-RaRa and BCR-ABL were detected by RT-PCR; and cellular features were analyzed by R-band in 304 patients. The patients were divided into three groups according to their immunophenotypes: AML with CD7 expression (CD7 group), AML with CD4 expression(CD4 group) and AML without CD7 and CD4 expression (common AML group)...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28017614/fto-plays-an-oncogenic-role-in-acute-myeloid-leukemia-as-a-n-6-methyladenosine-rna-demethylase
#9
Zejuan Li, Hengyou Weng, Rui Su, Xiaocheng Weng, Zhixiang Zuo, Chenying Li, Huilin Huang, Sigrid Nachtergaele, Lei Dong, Chao Hu, Xi Qin, Lichun Tang, Yungui Wang, Gia-Ming Hong, Hao Huang, Xiao Wang, Ping Chen, Sandeep Gurbuxani, Stephen Arnovitz, Yuanyuan Li, Shenglai Li, Jennifer Strong, Mary Beth Neilly, Richard A Larson, Xi Jiang, Pumin Zhang, Jie Jin, Chuan He, Jianjun Chen
N(6)-Methyladenosine (m(6)A) represents the most prevalent internal modification in mammalian mRNAs. Despite its functional importance in various fundamental bioprocesses, the studies of m(6)A in cancer have been limited. Here we show that FTO, as an m(6)A demethylase, plays a critical oncogenic role in acute myeloid leukemia (AML). FTO is highly expressed in AMLs with t(11q23)/MLL rearrangements, t(15;17)/PML-RARA, FLT3-ITD, and/or NPM1 mutations. FTO enhances leukemic oncogene-mediated cell transformation and leukemogenesis, and inhibits all-trans-retinoic acid (ATRA)-induced AML cell differentiation, through regulating expression of targets such as ASB2 and RARA by reducing m(6)A levels in these mRNA transcripts...
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/27899039/sensitive-monitoring-of-acute-promyelocytic-leukemia-by-pml-rara-dna-q-pcr
#10
Ivar O Kommers, Paul A Bartley, Bradley Budgen, Sue Latham, Ashanka Beligaswatte, Shane G Supple, Alberto Catalano, Harry J Iland, Alexander A Morley, David M Ross
No abstract text is available yet for this article.
November 30, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27740626/the-lncrna-hotairm1-regulates-the-degradation-of-pml-rara-oncoprotein-and-myeloid-cell-differentiation-by-enhancing-the-autophagy-pathway
#11
Zhen-Hua Chen, Wen-Tao Wang, Wei Huang, Ke Fang, Yu-Meng Sun, Shu-Rong Liu, Xue-Qun Luo, Yue-Qin Chen
Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are of great importance in different cell contexts. However, only a very small number of lncRNAs have been experimentally validated and functionally annotated during human hematopoiesis. Here, we report an lncRNA, HOTAIRM1, which is associated with myeloid differentiation and has pivotal roles in the degradation of oncoprotein PML-RARA and in myeloid cell differentiation by regulating autophagy pathways. We first revealed that HOTAIRM1 has different variants that are expressed at different levels in cells and that the expression pattern of HOTAIRM1 is closely related to that of the PML-RARA oncoprotein in acute promyelocytic leukemia (APL) patients...
February 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27728571/acute-myeloid-leukemia-microgranular-variant-pml-rara-negative
#12
V T Premkumar, Sooriyakumar, Sivaramasubramanian, Muralidharan, Dhanus Sadasivan Nair
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/27708545/chromosomal-abnormality-of-acute-promyelocytic-leukemia-other-than-pml-rara-a-case-report-of-acute-promyelocytic-leukemia-with-del-5q
#13
Osamu Imataki, Makiko Uemura
BACKGROUND: The recent study described a better outcome in acute promyelocytic leukemia patients treated with all-trans retinoic acid and arsenic oxide compared to those treated with all-trans retinoic acid combined with conventional chemotherapy. The pivotal study indicated that favorable-risk acute promyelocytic leukemia patients can be cured without any cytotoxic chemotherapy. Even high-risk patients are treatable with cytotoxic agents. Acute promyelocytic leukemia does not develop only by the dedifferentiation caused by PML-RARA...
2016: BMC Clinical Pathology
https://www.readbyqxmd.com/read/27694499/the-complex-relationship-of-tribbles-pseudokinase-1-pml-rara-and-c-ebp%C3%AE-in-leukemia-two-possible-couples-but-not-a-trio
#14
EDITORIAL
Guillermo Velasco
No abstract text is available yet for this article.
October 2016: Haematologica
https://www.readbyqxmd.com/read/27632978/multiplexed-automated-digital-quantification-of-fusion-transcripts-comparative-study-with-fluorescent-in-situ-hybridization-fish-technique-in-acute-leukemia-patients
#15
COMPARATIVE STUDY
Ariz Akhter, Muhammad Kashif Mughal, Ghaleb Elyamany, Gary Sinclair, Raja Zahratul Azma, Noraidah Masir, Salwati Shuib, Fariborz Rashid-Kolvear, Meer-Taher Shabani-Rad, Douglas Allan Stewart, Adnan Mansoor
BACKGROUND: The World Health Organization (WHO) classification system defines recurrent chromosomal translocations as the sole diagnostic and prognostic criteria for acute leukemia (AL). These fusion transcripts are pivotal in the pathogenesis of AL. Clinical laboratories universally employ conventional karyotype/FISH to detect these chromosomal translocations, which is complex, labour intensive and lacks multiplexing capacity. Hence, it is imperative to explore and evaluate some newer automated, cost-efficient multiplexed technologies to accommodate the expanding genetic landscape in AL...
September 15, 2016: Diagnostic Pathology
https://www.readbyqxmd.com/read/27626703/pml-rara-inhibits-pten-expression-in-hematopoietic-cells-by-competing-with-pu-1-transcriptional-activity
#16
Nélida Inés Noguera, Maria Liliana Piredda, Riccardo Taulli, Gianfranco Catalano, Giulia Angelini, Girish Gaur, Clara Nervi, Maria Teresa Voso, Andrea Lunardi, Pier Paolo Pandolfi, Francesco Lo-Coco
Acute promyelocitic leukemia (APL) is characterized by the pathognomonic presence in leukemic blasts of the hybrid protein PML/RARA, that acts as a transcriptional repressor impairing the expression of genes that are critical to myeloid differentiation. Here, we show that primary blasts from APL patients express lower levels of the oncosuppressor protein PTEN, as compared to blast cells from other AML subtypes or normal bone marrow, and demonstrate that PML-RARA directly inhibits PTEN expression. We show that All-Trans Retinoic Acid (ATRA) triggers in APL cells an active chromatin status at the core regulatory region of the PTEN promoter, that allows the binding of the myeloid-regulating transcription factor PU...
October 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27626069/evolution-of-a-flt3-tkd-mutated-subclone-at-meningeal-relapse-in-acute-promyelocytic-leukemia
#17
Tilmann Bochtler, Stefan Fröhling, Wilko Weichert, Volker Endris, Christian Thiede, Barbara Hutter, Michael Hundemer, Anthony D Ho, Alwin Krämer
Here, we report the case of an acute promyelocytic leukemia (APL) patient who-although negative for FLT3 mutations at diagnosis-developed isolated FLT3 tyrosine kinase II domain (FLT3-TKD)-positive meningeal relapse, which, in retrospect, could be traced back to a minute bone marrow subclone present at first diagnosis. Initially, the 48-yr-old female diagnosed with high-risk APL had achieved complete molecular remission after standard treatment with all-trans retinoic acid (ATRA) and chemotherapy according to the AIDA (ATRA plus idarubicin) protocol...
September 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27560113/rationale-and-efficacy-of-proteasome-inhibitor-combined-with-arsenic-trioxide-in-the-treatment-of-acute-promyelocytic-leukemia
#18
S Ganesan, A A Alex, E Chendamarai, N Balasundaram, H K Palani, S David, U Kulkarni, M Aiyaz, R Mugasimangalam, A Korula, A Abraham, A Srivastava, R A Padua, C Chomienne, B George, P Balasubramanian, V Mathews
Arsenic trioxide (ATO) mediates PML-RARA (promyelocytic leukemia-retinoic acid receptor-α) oncoprotein degradation via the proteasome pathway and this degradation appears to be critical for achieving cure in acute promyeloytic leukemia (APL). We have previously demonstrated significant micro-environment-mediated drug resistance (EMDR) to ATO in APL. Here we demonstrate that this EMDR could be effectively overcome by combining a proteasome inhibitor (bortezomib) with ATO. A synergistic effect on combining these two agents in vitro was noted in both ATO-sensitive and ATO-resistant APL cell lines...
November 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27507651/comment-on-sumo-deconjugation-is-required-for-arsenic-triggered-ubiquitylation-of-pml
#19
Omar Ferhi, Laurent Pérès, Sarah Tessier, Hugues de Thé, Valérie Lallemand-Breitenbach
Fasci et al proposed that a SENP1-mediated switch from SUMO2 to SUMO1 conjugation on Lys(65) in promyelocytic leukemia protein (PML) is required for arsenic-induced PML degradation, the basis for the antileukemic activity of arsenic. We found that PML or PML/RARA (retinoic acid receptor α) mutants that cannot be SUMO-conjugated on this specific site nevertheless underwent immediate arsenic-triggered SUMO modification. Moreover, these mutants were efficiently degraded in cells and even in vivo, demonstrating that SUMOylation of Lys(65) was dispensable for arsenic response...
2016: Science Signaling
https://www.readbyqxmd.com/read/27468869/incidence-of-preleukemic-fusion-genes-in-healthy-subjects
#20
P Kosik, M Skorvaga, I Belyaev
The diagnostics of leukemia relies upon multi-parametric approach involving a number of different pathology disciplines such as flow cytometry, histopathology, cytogenetics and molecular genetics [fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR)]. Childhood leukemia is often determined by the presence of specific chromosomal translocation that entails the generation of preleukemic fusion genes (PFG). In the last two decades, several studies have reported observations that PFG are present in healthy population and not necessarily result in leukemia...
2016: Neoplasma
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