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https://www.readbyqxmd.com/read/28810325/-heterogeneity-and-clonal-evolution-in-pediatric-etv6-runx1-acute-lymphoblastic-leukemia-by-quantitative-multigene-fluorescence-in-situ-hybridization
#1
L Zhang, L P Hu, X M Liu, Y Guo, W Y Yang, J Y Zhang, F Liu, T F Liu, S C Wang, X J Chen, M Ruan, B Q Qi, L X Chang, Y M Chen, Y Zou, X F Zhu
Objective: To evaluate heterogeneity and clonal evolution in pediatric ETV6-RUNX1(+) acute lymphoblastic leukemia (ALL) in China. Methods: Totally 48 children (<14 years) with newly diagnosed ETV6-RUNX1(+) ALL in Institute of Hematology and Blood Disease Hospital, CAMS and PUMC, from February 2006 to June 2011 were included. The copy number variations were analyzed by quantitative multigene fluorescence in situ hybridization (QM-FISH) in 48 patients. Non-normal distribution of measurement data were shown with Median (range) , count data were shown with percent (%) ...
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28807942/nuclear-fak-and-runx1-cooperate-to-regulate-igfbp3-cell-cycle-progression-and-tumor-growth
#2
Marta Canel, Adam Byron, Andrew H Sims, Jessy Cartier, Hitesh Patel, Margaret C Frame, Valerie G Brunton, Bryan Serrels, Alan Serrels
Nuclear focal adhesion kinase (FAK) is a potentially important regulator of gene expression in cancer, impacting both cellular function and the composition of the surrounding tumor microenvironment. Here we report in a murine model of skin squamous cell carcinoma (SCC) that nuclear FAK regulates Runx1-dependent transcription of insulin-like growth factor binding protein 3 (IGFBP3), and that this regulates SCC cell cycle progression and tumor growth in vivo. Furthermore, we identified a novel molecular complex between FAK and Runx1 in the nucleus of SCC cells and showed that FAK interacted with a number of Runx1 regulatory proteins, including Sin3a and other epigenetic modifiers known to alter Runx1 transcriptional function through post-translational modification...
August 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28806978/transcriptome-sequencing-in-pediatric-acute-lymphoblastic-leukemia-identifies-fusion-genes-associated-with-distinct-dna-methylation-profiles
#3
Yanara Marincevic-Zuniga, Johan Dahlberg, Sara Nilsson, Amanda Raine, Sara Nystedt, Carl Mårten Lindqvist, Eva C Berglund, Jonas Abrahamsson, Lucia Cavelier, Erik Forestier, Mats Heyman, Gudmar Lönnerholm, Jessica Nordlund, Ann-Christine Syvänen
BACKGROUND: Structural chromosomal rearrangements that lead to expressed fusion genes are a hallmark of acute lymphoblastic leukemia (ALL). In this study, we performed transcriptome sequencing of 134 primary ALL patient samples to comprehensively detect fusion transcripts. METHODS: We combined fusion gene detection with genome-wide DNA methylation analysis, gene expression profiling, and targeted sequencing to determine molecular signatures of emerging ALL subtypes...
August 14, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28801348/incidental-detection-of-germline-variants-of-potential-clinical-significance-by-massively-parallel-sequencing-in-haematological-malignancies
#4
Costas K Yannakou, Kate Jones, Georgina L Ryland, Ella R Thompson, Gareth Reid, Michelle McBean, Alison Trainer, David Westerman, Piers Blombery
Massively parallel sequencing (MPS) technology has become routinely available for diagnosis, prognostication and therapeutic decision-making in haematological malignancies. However, increased throughput and wider coverage of genes can have unintended consequences. Germline variants of potential clinical significance (GVPCSs) detected during cancer testing may have implications for patients and families beyond the biological evaluation of a specific tumour. 721 reports generated from MPS panels used in the routine testing of myeloid and lymphoid malignancies were reviewed and variants within genes of potential germline relevance (TP53, RUNX1, GATA2 and WT1 in all contexts and CBL, KRAS and NRAS in the setting of juvenile myelomonocytic leukaemia) were analysed...
August 11, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28790107/runx1-is-required-for-oncogenic-myb-and-myc-enhancer-activity-in-t-cell-acute-lymphoblastic-leukemia
#5
AHyun Choi, Anuradha Illendula, John A Pulikkan, Justine E Roderick, Jessica Tesell, Jun Yu, Nicole Hermance, Lihua Julie Zhu, Lucio H Castilla, John H Bushweller, Michelle A Kelliher
The gene encoding the RUNX1 transcription factor is mutated in a subset of T cell acute lymphoblastic leukemia (T-ALL) patients and RUNX1 mutations are associated with a poor prognosis. These mutations cluster in the DNA binding Runt domain, are thought to represent loss-of-function mutations, indicating that RUNX1 suppresses T cell transformation. RUNX1 has been proposed to have tumor suppressor roles in TLX1/3 transformed human T-ALL cell lines and NOTCH1 T-ALL mouse models. Yet retroviral insertional mutagenesis screens identify RUNX genes as collaborating oncogenes in MYC-driven leukemia mouse models...
August 8, 2017: Blood
https://www.readbyqxmd.com/read/28765611/the-differentiation-of-ror-%C3%AE-t-expressing-inkt17-cells-is-orchestrated-by-runx1
#6
Puspa Thapa, Bryce Manso, Ji Young Chung, Sinibaldo Romera Arocha, Hai-Hui Xue, Derek B Sant' Angelo, Virginia Smith Shapiro
iNKT cells are a unique lineage of T cells that recognize glycolipid presented by CD1d. In the thymus, they differentiate into iNKT1, iNKT2 and iNKT17 effector subsets, characterized by preferential expression of Tbet, Gata3 and ROR-γt and production of IFN-γ, IL-4 and IL-17, respectively. We demonstrate that the transcriptional regulator Runx1 is essential for the generation of ROR-γt expressing iNKT17 cells. PLZF-cre Runx1 cKO mice lack iNKT17 cells in the thymus, spleen and liver. Runx1-deficient iNKT cells have altered expression of several genes important for iNKT17 differentiation, including decreased expression of IL-7Rα, BATF and c-Maf and increased expression of Bcl11b and Lef1...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28751771/number-of-runx1-mutations-wild-type-allele-loss-and-additional-mutations-impact-on-prognosis-in-adult-runx1-mutated-aml
#7
A Stengel, W Kern, M Meggendorfer, N Nadarajah, K Perglerovà, T Haferlach, C Haferlach
RUNX1 mutated AML show a distinct pattern of genetic abnormalities and an adverse prognosis. We analyzed the impact of multiple RUNX1 mutations and RUNX1 wild-type (WT) loss in 467 AML with RUNX1 mutations (mut): (1) RUNX1 WT loss (n=53), (2) >1 RUNX1mut (n=94) and (3) 1 RUNX1mut (n=323). In 1 RUNX1mut, +8 was most frequent, whereas in WT loss +13 was the most abundant trisomy (+8: 66% vs. 31%, P=0.022; +13: 15% vs 62%, P<0.001). Analyses of 28 genes in 163 selected cases revealed SRSF2 (39%), ASXL1 (36%), DNMT3A (19%), IDH2 (17%) and SF3B1 (17%) as most frequently mutated genes...
July 28, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28747748/the-epigenetic-landscape-of-promoter-genome-wide-analysis-in-breast-cancer
#8
Seher Karsli-Ceppioglu, Aslihan Dagdemir, Gaëlle Judes, André Lebert, Frédérique Penault-Llorca, Yves-Jean Bignon, Dominique Bernard-Gallon
Breast cancer is a heterogeneous disease due to its clinico-pathological features and response to therapy. The classification of breast tumors based on their hormone receptor status and pathologic features. Post-translational histone modifications come into prominence for regulation of gene expression in cancer pathogenesis. Here, we analyzed dysregulation of H3K9ac and H3K27me3-enriched subtype-specific genes using ChIP-on-chip assay in breast cancer tumors and matched normal tissue samples. Breast cancer tumors were classified according to St Gallen Consensus 2013...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28744012/b7-h4-enhances-the-differentiation-of-murine-leukemia-initiating-cells-via-the-pten-akt-rcor2-runx1-pathways
#9
F Xia, Y Zhang, L Xie, H Jiang, H Zeng, C Chen, L Liu, X He, X Hao, X Fang, X Liu, F Zhang, H Gu, J Wan, Y Cheng, C C Zhang, G-Q Chen, Y Lu, Z Yu, J Zheng
Leukemia accepted article preview online, 24 July 2017. doi:10.1038/leu.2017.232.
July 24, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28735486/detection-and-quantification-of-acute-myeloid-leukemia-associated-fusion-transcripts
#10
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/28729333/choosing-wisely-runx1-alternate-promoter-use
#11
Alan B Cantor
No abstract text is available yet for this article.
July 20, 2017: Blood
https://www.readbyqxmd.com/read/28724437/the-lncrna-casc15-regulates-sox4-expression-in-runx1-rearranged-acute-leukemia
#12
Thilini R Fernando, Jorge R Contreras, Matteo Zampini, Norma I Rodriguez-Malave, Michael O Alberti, Jaime Anguiano, Tiffany M Tran, Jayanth K Palanichamy, Jasmine Gajeton, Nolan M Ung, Cody J Aros, Ella V Waters, David Casero, Giuseppe Basso, Martina Pigazzi, Dinesh S Rao
BACKGROUND: Long non-coding RNAs (lncRNAs) play a variety of cellular roles, including regulation of transcription and translation, leading to alterations in gene expression. Some lncRNAs modulate the expression of chromosomally adjacent genes. Here, we assess the roles of the lncRNA CASC15 in regulation of a chromosomally nearby gene, SOX4, and its function in RUNX1/AML translocated leukemia. RESULTS: CASC15 is a conserved lncRNA that was upregulated in pediatric B-acute lymphoblastic leukemia (B-ALL) with t (12; 21) as well as pediatric acute myeloid leukemia (AML) with t (8; 21), both of which are associated with relatively better prognosis...
July 19, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28723564/the-lysine-acetyltransferase-gcn5-is-required-for-inkt-cell-development-through-egr2-acetylation
#13
Yajun Wang, Chawon Yun, Beixue Gao, Yuanming Xu, Yana Zhang, Yiming Wang, Qingfei Kong, Fang Zhao, Chyung-Ru Wang, Sharon Y R Dent, Jian Wang, Xiangping Xu, Hua-Bin Li, Deyu Fang
The development of CD1d-restricted invariant natural killer T (iNKT) cells, a population that is critical for both innate and adaptive immunity, is regulated by multiple transcription factors, but the molecular mechanisms underlying how the transcriptional activation of these factors are regulated during iNKT development remain largely unknown. We found that the histone acetyltransferase general control non-derepressible 5 (GCN5) is essential for iNKT cell development during the maturation stage. GCN5 deficiency blocked iNKT cell development in a cell-intrinsic manner...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28720763/high-frequency-of-runx1-mutation-in-myelodysplastic-syndrome-patients-with-whole-arm-translocation-of-der-1-7-q10-p10
#14
T Zhang, Y Xu, J Pan, H Li, Q Wang, L Wen, D Wu, A Sun, S Chen
Leukemia accepted article preview online, 19 July 2017. doi:10.1038/leu.2017.228.
July 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28709134/bcr-abl1-like-acute-lymphoblastic-leukaemia-from-bench-to-bedside
#15
REVIEW
Judith M Boer, Monique L den Boer
Acute lymphoblastic leukaemia (ALL) occurs in approximately 1:1500 children and is less frequently found in adults. The most common immunophenotype of ALL is the B cell lineage and within B cell precursor ALL, specific genetic aberrations define subtypes with distinct biological and clinical characteristics. With more advanced genetic analysis methods such as whole genome and transcriptome sequencing, novel genetic subtypes have recently been discovered. One novel class of genetic aberrations comprises tyrosine kinase-activating lesions, including translocations and rearrangements of tyrosine kinase and cytokine receptor genes...
July 11, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28708822/an-ancient-neurotrophin-receptor-code-a-single-runx-cbf%C3%AE-complex-determines-somatosensory-neuron-fate-specification-in-zebrafish
#16
Philia Gau, Andrew Curtright, Logan Condon, David W Raible, Ajay Dhaka
In terrestrial vertebrates such as birds and mammals, neurotrophin receptor expression is considered fundamental for the specification of distinct somatosensory neuron types where TrkA, TrkB and TrkC specify nociceptors, mechanoceptors and proprioceptors/mechanoceptors, respectively. In turn, Runx transcription factors promote neuronal fate specification by regulating neurotrophin receptor and sensory receptor expression where Runx1 mediates TrkA+ nociceptor diversification while Runx3 promotes a TrkC+ proprioceptive/mechanoceptive fate...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28704388/the-mir-23a-27a-24-2-microrna-cluster-buffers-transcription-and-signaling-pathways-during-hematopoiesis
#17
Jeffrey L Kurkewich, Justin Hansen, Nathan Klopfenstein, Helen Zhang, Christian Wood, Austin Boucher, Joseph Hickman, David E Muench, H Leighton Grimes, Richard Dahl
MicroRNA cluster mirn23a has previously been shown to promote myeloid development at the expense of lymphoid development in overexpression and knockout mouse models. This polarization is observed early in hematopoietic development, with an increase in common lymphoid progenitors (CLPs) and a decrease in all myeloid progenitor subsets in adult bone marrow. The pool size of multipotential progenitors (MPPs) is unchanged; however, in this report we observe by flow cytometry that polarized subsets of MPPs are changed in the absence of mirn23a...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28698845/intrachromosomal-amplification-of-chromosome-21-in-korean-pediatric-patients-with-b-cell-precursor-acute-lymphoblastic-leukemia-in-a-single-institution
#18
Mina Yang, Eun Sang Yi, Hee Jin Kim, Keon Hee Yoo, Hong Hoe Koo, Sun-Hee Kim
BACKGROUND: Intrachromosomal amplification of chromosome 21 (iAMP21), defined as the presence of three or more RUNX1 signals on one marker chromosome, is a distinct cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) that is known to have a poor prognosis when treated with standard therapy. The aim of this study was to evaluate the clinical characteristics of Korean children with iAMP21. METHODS: The cytogenetic data from BCP-ALL children were reviewed...
June 2017: Blood Research
https://www.readbyqxmd.com/read/28698281/mir-27b-augments-bone-marrow-progenitor-cell-survival-via-suppressing-the-mitochondrial-apoptotic-pathway-in-type-2-diabetes
#19
Hainan Li, Jenney Liu, Yihan Wang, Zhiyao Fu, Maik Huttemann, Terrence J Monks, Alex F Chen, Jie-Mei Wang
INTRODUCTION: Bone marrow derived progenitor cells (BMPCs) are potential candidates for autologous cell therapy in tissue repair because of their high angiogenic potential. However, increased progenitor cell apoptosis in diabetes directly limits their success in the clinic. MicroRNAs are endogenous non-coding RNAs that regulate gene expression at the post-transcriptional level, but their roles in BMPC-mediated angiogenesis are incompletely understood. In the present study, we tested the hypothesis that the pro-angiogenic miR-27b inhibits BMPC apoptosis in type 2 diabetes...
July 11, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28693140/acute-myeloid-leukemia-with-t-3-21-q26-2-q22-developing-following-low-dose-methotrexate-therapy-for-rheumatoid-arthritis-and-expressing-two-aml1-mds1-evi1-fusion-proteins-a-case-report
#20
Keisuke Tanaka, Gaku Oshikawa, Hiroki Akiyama, Shinya Ishida, Toshikage Nagao, Masahide Yamamoto, Osamu Miura
The t(3;21)(q26.2;q22) translocation is a rare chromosomal abnormality exhibited almost exclusively in therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) or in the blastic crisis phase of chronic myelogenous leukemia, which results in the fusion of the runt related transcription factor 1 (RUNX1, also called AML1) gene at 21q22 to the myelodysplasia syndrome 1 (MDS1)-ecotropic virus integration site 1 (EVI1) complex locus (MECOM) at 3q26.2, generating various fusion transcripts, including AML1/MDS1/EVI1 (AME)...
July 2017: Oncology Letters
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