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https://www.readbyqxmd.com/read/29214878/combination-of-ikzf1-deletion-and-early-molecular-response-show-significant-roles-on-prognostic-stratification-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-patients
#1
He Li, Wanhua Zhang, Pu Kuang, Yuanxin Ye, Jinjun Yang, Yang Dai, Xiaojun Lu, Yuhuan Zheng, Ting Liu
We retrospectively analyzed the samples collected from 66 patients with Ph+ALL enrolled on ChiCTR-TNRC-09000309 clinical trial. CR rate was 95.5%, and estimated 2-year OS and DFS were 51.7 ± 11.7% and 26.9 ± 11.6%, 3-year OS and DFS were 31.6 ± 12.0% and 23.4 ± 11.6%. By combining IKZF1 deletion and early molecular responses, we redefined the patients as low, intermediate, and high risk 3 groups separately. Patients with double negative in IKZF1 and early molecular response experienced significant superior survival, while patients with double positive would have the worst outcome, and patients who were one or the other with IKZF1 deletion or MRD status had intermediate outcome...
December 7, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29204341/case-report-exome-sequencing-identifies-t-all-with-myeloid-features-as-a-ikzf1-struck-early-precursor-t-cell-malignancy
#2
Marcus C Hansen, Line Nederby, Eigil Kjeldsen, Marianne A Petersen, Hans B Ommen, Peter Hokland
No abstract text is available yet for this article.
2018: Leukemia Research Reports
https://www.readbyqxmd.com/read/29199525/molecular-genetic-profile-in-bcr-abl1-negative-pediatric-b-cell-acute-lymphoblastic-leukemia-can-further-refine-outcome-prediction-in-addition-to-that-by-end-induction-minimal-residual-disease-detection
#3
Sanjeev Kumar Gupta, Sameer Bakhshi, Anita Chopra, Vineet Kumar Kamal
The recently proposed molecular genetic criteria promise improved risk-prediction in B-cell acute lymphoblastic leukemia (B-ALL). This study assesses their utility in BCR-ABL1 negative pediatric B-ALL, particularly with respect to end-induction minimal residual disease (MRD). The DNA was analyzed for copy number alterations in CDKN2A/B, PAX5, IKZF1, and other genes. Seventy-six cases with median age 7 years (2 months-18 years) included MRD-positive (24; 32%), and MRD negative-standard (20; 26%), intermediate (20; 26%), & high risk (12;16%) cases...
December 3, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29194562/a-risk-score-including-microdeletions-improves-relapse-prediction-for-standard-and-medium-risk-precursor-b-cell-acute-lymphoblastic-leukaemia-in-children
#4
Rosemary Sutton, Nicola C Venn, Tamara Law, Judith M Boer, Toby N Trahair, Anthea Ng, Monique L Den Boer, Anuruddhika Dissanayake, Jodie E Giles, Pauline Dalzell, Chelsea Mayoh, Draga Barbaric, Tamas Revesz, Frank Alvaro, Rob Pieters, Michelle Haber, Murray D Norris, Martin Schrappe, Luciano Dalla Pozza, Glenn M Marshall
To prevent relapse, high risk paediatric acute lymphoblastic leukaemia (ALL) is treated very intensively. However, most patients who eventually relapse have standard or medium risk ALL with low minimal residual disease (MRD) levels. We analysed recurrent microdeletions and other clinical prognostic factors in a cohort of 475 uniformly treated non-high risk precursor B-cell ALL patients with the aim of better predicting relapse and refining risk stratification. Lower relapse-free survival at 7 years (RFS) was associated with IKZF1 intragenic deletions (P < 0·0001); P2RY8-CRLF2 gene fusion (P < 0·0004); Day 33 MRD>5 × 10-5 (P < 0·0001) and High National Cancer Institute (NCI) risk (P < 0·0001)...
November 30, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29050694/the-biology-of-philadelphia-chromosome-like-all
#5
REVIEW
Kathryn G Roberts
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a recently described subtype of B-cell precursor ALL with a gene expression profile similar to Ph-positive ALL and a high frequency of IKZF1 alterations. The prevalence of Ph-like ALL increases with age, ranging from 10-15% of children to over 25% of young adults with ALL. It occurs more frequently in males and is associated with adverse clinical features including elevated minimal residual disease levels and poor survival in both children and adults...
September 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/28960754/genetic-heterogeneity-of-uncharacterized-childhood-autoimmune-diseases-with-lymphoproliferation
#6
Masatoshi Takagi, Akihiro Hoshino, Kenichi Yoshida, Hiroo Ueno, Kohsuke Imai, Jinhua Piao, Hirokazu Kanegane, Motoi Yamashita, Tsubasa Okano, Hideki Muramatsu, Yusuke Okuno, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Seishi Ogawa, Yasuhide Hayashi, Seiji Kojima, Tomohiro Morio
Autoimmune diseases in children are rare and can be difficult to diagnose.  Single causative genes have been identified for some pediatric autoimmune diseases. Such orphan diseases may not be diagnosed properly due to the variability of patients' phenotypes. Guidelines for the diagnostic process need to be developed. Fifteen patients with uncharacterized childhood autoimmune diseases with lymphoproliferation that had negative testing for autoimmune lymphoproliferative syndrome were subjected to whole-exome sequencing to identify genes associated with these conditions...
September 29, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28947432/ikzf1-gene-in-childhood-b-cell-precursor-acute-lymphoblastic-leukemia-interplay-between-genetic-susceptibility-and-somatic-abnormalities
#7
Bruno Almeida Lopes, Thayana Conceicao Barbosa, Bruna Kelly Santos Souza, Caroline Pires Poubel, Maria S Pombo-de-Oliveira, Mariana Emerenciano
Single nucleotide polymorphisms (SNPs) in IKZF1 are associated with inherited susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Besides, somatic copy number abnormalities (CNAs) in genes related to lymphopoiesis (e.g. IKZF1, CDKN2A/B, BTG1) impact patient's outcome. Therefore, this study aimed to investigate an association between germline susceptibility and CNAs in BCP-ALL. The IKZF1 SNPs (rs11978267 and rs4132601) were genotyped in 276 cases and 467 controls. Bone marrow samples were used to determine the presence of somatic abnormalities...
September 25, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28927821/a-novel-ikaros-haploinsufficiency-kindred-with-unexpectedly-late-and-variable-b-cell-maturation-defects
#8
Delfien J Bogaert, Hye Sun Kuehn, Carolien Bonroy, Katherine R Calvo, Joke Dehoorne, Arnaud V Vanlander, Marieke De Bruyne, Urszula Cytlak, Venetia Bigley, Frans De Baets, Elfride De Baere, Sergio D Rosenzweig, Filomeen Haerynck, Melissa Dullaers
We report on the first truncating IKZF1 mutation associated with IKAROS haploinsufficiency and illustrate an unexpectedly late and variable block in central and peripheral B cell development in two patients and their asymptomatic mother.
September 16, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28927157/selected-mirna-levels-are-associated-with-ikzf1-microdeletions-in-pediatric-acute-lymphoblastic-leukemia
#9
J Krzanowski, J Madzio, A Pastorczak, A Tracz, M Braun, J Tabarkiewicz, A Pluta, W Młynarski, I Zawlik
The clinical outcome of children with high-risk relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is poor. The present study assessed the utility and prognostic value of selected microRNA (miRNA/miR) in BCP-ALL. The changes in the expression levels of these miRNAs regarding known gene lesions affecting lymphoid development [early B-cell factor 1 (EBF1), ETS variant 6 (ETV6), IKAROS family zinc finger 1 (IKZF1), paired box 5 (PAX5), cyclin dependent kinase inhibitor (CDKN) 2A/CDKN2B, retinoblastoma 1 (RB1), pseudoautosomal region 1 (PAR1), B-cell translocation gene 1 protein (BTG1)] were analyzed...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927072/arsenic-trioxide-potentiates-sensitivity-of-multiple-myeloma-cells-to-lenalidomide-by-upregulating-cereblon-expression-levels
#10
Yuan Jian, Wen Gao, Chuanying Geng, Huixing Zhou, Yun Leng, Yanchen Li, Wenming Chen
The mechanism of the anti-myeloma effect of the immunomodulatory drug lenalidomide relies upon the binding of lenalidomide or an analogue to cereblon (CRBN) ubiquitin ligase, which inhibits it and results in the degradation of Ikaros-family zinc finger proteins 1 and 3 (IKZF1 and IKZF3). To determine whether the traditional Chinese medicine arsenic trioxide, could potentiate sensitivity of multiple myeloma (MM) cells to lenalidomide and identify the mechanism by which this happens, the present study investigated how arsenic trioxide affected CRBN on MM cell lines and examined the anti-myeloma effect and mechanism in the combination of arsenic trioxide and lenalidomide...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28914974/mucocutaneous-inflammation-in-the-ikaros-family-zinc-finger-1-ikzf1-keratin-5-specifc-transgenic-mice
#11
Mayumi Ueta, Junji Hamuro, Hiromi Nishigaki, Naomi Nakamura, Katsuhiko Shinomiya, Katsura Mizushima, Yuki Hitomi, Risa Tamagawa-Mineoka, Norihiko Yokoi, Yuji Naito, Katsushi Tokunaga, Norito Katoh, Chie Sotozono, Shigeru Kinoshita
BACKGROUND: Our genome-wide association study documented an association between cold medicine related Stevens-Johnson syndrome / toxic epidermal necrolysis (CM-SJS/TEN) and Ikaros Family Zinc Finger 1 (IKZF1). Few studies examined biological and pathological functions of IKZF1 in mucosal immunity. We hypothesized that IKZF1 contributes to the mucocutaneous inflammation. METHODS: Human skin and conjunctival tissues were obtained for immunohistological studies. Primary human conjunctival epithelial cells (PHCjECs) and adult human epidermal keratinocytes (HEKa) also used for gene expression analysis...
September 15, 2017: Allergy
https://www.readbyqxmd.com/read/28905228/genetic-susceptibility-in-childhood-acute-lymphoblastic-leukemia
#12
REVIEW
Angela Gutierrez-Camino, Idoia Martin-Guerrero, Africa García-Orad
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and a leading cause of death due to disease in children. The genetic basis of ALL susceptibility has been supported by its association with certain congenital disorders and, more recently, by several genome-wide association studies (GWAS). These GWAS identified common variants in ARID5B, IKZF1, CEBPE, CDKN2A, PIP4K2A, LHPP and ELK3 influencing ALL risk. However, the risk variants of these SNPs were not validated in all populations, suggesting that some of the loci could be population specific...
September 13, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28886309/the-correlation-between-pax5-deletion-and-patients-survival-in-iranian-children-with-precursor-b-cell-acute-lymphocytic-leukemia
#13
A Moafi, A Zojaji, R Salehi, S Najafi Dorcheh, S Rahgozar
Despite advances in treatment, children with acute lymphoblastic leukemia (ALL) still experience drug resistance and relapse. Several gene mutations are involved in the onset of this disease and resistance to therapy. The present study examines the incidence of IKZF1, CDKN2A/B, PAX5, EBF1, ETV6, BTG1, RB1, JAK2, and Xp22.33 gene deletions/duplications associated with pediatric ALL in Iran and investigates the possible effect of these mutations on drug resistance. Three-year disease-free survival (3DFS) was evaluated for children diagnosed with Philadelphia negative precursor-B-cell ALL hospitalized at Sayed-al-Shohada Hospital, Isfahan-Iran, from January 2009 until December 2012...
August 30, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28879630/polymorphism-in-ikzf1-gene-affects-clinical-outcome-in-diffuse-large-b-cell-lymphoma
#14
Marta Bielska, Maciej Borowiec, Dorota Jesionek-Kupnicka, Marcin Braun, Marcin Bojo, Agata Pastorczak, Ewa Kalinka-Warzocha, Monika Prochorec-Sobieszek, Tadeusz Robak, Krzysztof Warzocha, Wojciech Młynarski, Ewa Lech-Marańda
IKZF1 encodes a transcription factor involved in B-cell maturation and differentiation. We genotyped 218 diffuse large B-cell lymphoma (DLBCL) patients and 715 unrelated controls using a TaqMan allelic discrimination assay. No statistical difference was observed in the genotype distribution of the IKZF1 rs4132601 polymorphism between DLBCL patients and controls. However, the 2-year PFS rate of patients with the IKZF1 TT genotype was 54.3% compared to 68.6% in those with the IKZF1 G+ genotypes. Moreover, the IKZF1 rs4132601 polymorphism retained its independent prognostic impact on PFS...
December 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28866095/differential-expression-of-muc4-gpr110-and-il2ra-defines-two-groups-of-crlf2-rearranged-acute-lymphoblastic-leukemia-patients-with-distinct-secondary-lesions
#15
Teresa Sadras, Susan L Heatley, Chung H Kok, Phuong Dang, Kate M Galbraith, Barbara J McClure, Walter Muskovic, Nicola C Venn, Sarah Moore, Michael Osborn, Tamas Revesz, Andrew S Moore, Timothy P Hughes, David Yeung, Rosemary Sutton, Deborah L White
CRLF2-rearrangements (CRLF2-r) occur frequently in Ph-like B-ALL, a high-risk ALL sub-type characterized by a signaling profile similar to Ph + ALL, however accumulating evidence indicates genetic heterogeneity within CRLF2-r ALL. We performed thorough genomic characterization of 35 CRLF2-r cases (P2RY8-CRLF2 n = 18; IGH-CRLF2 n = 17). Activating JAK2 mutations were present in 34% of patients, and a CRLF2-F232C mutation was identified in an additional 17%. IKZF1 deletions were detected in 63% of cases...
November 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28842136/philadelphia-chromosome-like-acute-lymphoblastic-leukemia
#16
REVIEW
Ching-Hon Pui, Kathryn G Roberts, Jun J Yang, Charles G Mullighan
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a recently described B-cell precursor ALL with a gene expression profile and a high frequency of IKZF1 gene alteration similar to that of Ph-positive ALL. Its prevalence is approximately 12% in children, 21% in adolescents (16-20 years of age), and 20% to 24% in adults older than 40 years, with a peak (27%) in young adults 21 to 39 years old. It occurs more often in male individuals and patients with Down syndrome. Ph-like ALL is overrepresented in those with Hispanic ethnicity and is associated with inherited genetic variants in GATA3 (rs3824662)...
August 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28768142/contributions-of-ikzf1-ddc-cdkn2a-cebpe-and-lmo1-gene-polymorphisms-to-acute-lymphoblastic-leukemia-in-a-yemeni-population
#17
Boshra Al-Absi, Muhammad F M Razif, Suzita M Noor, Riyadh Saif-Ali, Mohammed Aqlan, Sameer D Salem, Radwan H Ahmed, Sekaran Muniandy
BACKGROUND: Genome-wide and candidate gene association studies have previously revealed links between a predisposition to acute lymphoblastic leukemia (ALL) and genetic polymorphisms in the following genes: IKZF1 (7p12.2; ID: 10320), DDC (7p12.2; ID: 1644), CDKN2A (9p21.3; ID: 1029), CEBPE (14q11.2; ID: 1053), and LMO1 (11p15; ID: 4004). In this study, we aimed to conduct an investigation into the possible association between polymorphisms in these genes and ALL within a sample of Yemeni children of Arab-Asian descent...
October 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28758283/copy-number-profiling-of-adult-relapsed-b-cell-precursor-acute-lymphoblastic-leukemia-reveals-potential-leukemia-progression-mechanisms
#18
Jordi Ribera, Lurdes Zamora, Mireia Morgades, Mar Mallo, Neus Solanes, Montserrat Batlle, Susana Vives, Isabel Granada, Jordi Juncà, Roberto Malinverni, Eulàlia Genescà, Ramon Guàrdia, Santiago Mercadal, Lourdes Escoda, Joaquín Martinez-Lopez, Mar Tormo, Jordi Esteve, Marta Pratcorona, Carmen Martinez-Losada, Francesc Solé, Evarist Feliu, Josep-Maria Ribera
The outcome of relapsed adult acute lymphoblastic leukemia (ALL) remains dismal despite new therapeutic approaches. Previous studies analyzing relapse samples have shown a high degree of heterogeneity regarding gene alterations without an evident relapse signature. Bone marrow or peripheral blood samples from 31 adult B-cell precursor ALL patients at first relapse, and 21 paired diagnostic samples were analyzed by multiplex ligation probe-dependent amplification (MLPA). Nineteen paired diagnostic and relapse samples of these 21 patients were also analyzed by SNP arrays...
July 30, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28751559/loss-of-function-but-not-dominant-negative-intragenic-ikzf1-deletions-are-associated-with-an-adverse-prognosis-in-adult-bcr-abl-negative-acute-lymphoblastic-leukemia
#19
Benjamin Kobitzsch, Nicola Gökbuget, Stefan Schwartz, Richard Reinhardt, Monika Brüggemann, Andreas Viardot, Ralph Wäsch, Michael Starck, Eckhard Thiel, Dieter Hoelzer, Thomas Burmeister
Genetic alterations of the transcription factor IKZF1 ("IKAROS") are detected in around 15-30% of cases of BCR-ABL-negative B-cell precursor acute lymphoblastic leukemia. Different types of intragenic deletions have been observed, resulting in a functionally inactivated allele ("loss-of-function") or in "dominant-negative" isoforms. The prognostic impact of these alterations especially in adult acute lymphoblastic leukemia is not well defined. We analyzed 482 well-characterized cases of adult BCR-ABL-negative B-precursor acute lymphoblastic leukemia uniformly treated in the framework of the GMALL studies and detected IKZF1 alterations in 128 cases (27%)...
October 2017: Haematologica
https://www.readbyqxmd.com/read/28751478/novel-gene-and-network-associations-found-for-acute-lymphoblastic-leukemia-using-case-control-and-family-based-studies-in-multiethnic-populations
#20
Priyanka Nakka, Natalie P Archer, Heng Xu, Philip J Lupo, Benjamin J Raphael, Jun J Yang, Sohini Ramachandran
Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, suggesting that germline variants influence ALL risk. Although multiple genome-wide association (GWA) studies have identified variants predisposing children to ALL, it remains unclear whether genetic heterogeneity affects ALL susceptibility and how interactions within and among genes containing ALL-associated variants influence ALL risk.Methods: Here, we jointly analyzed two published datasets of case-control GWA summary statistics along with germline data from ALL case-parent trios...
October 2017: Cancer Epidemiology, Biomarkers & Prevention
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