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https://www.readbyqxmd.com/read/28883285/genetic-abnormalities-in-core-binding-factor-acute-myeloid-leukemia
#1
Yuichi Ishikawa
Acute myeloid leukemia (AML) is a genetically heterogeneous disease, and its prognosis is stratified on the basis of chromosomal and genetic alterations. Core binding factor (CBF) leukemia consists of AML with t (8;21) (p22;q22) and inv16 (q16q16) /t (16;16) (q16;q16) and is included in AML with recurrent genetic abnormality according to WHO classification. Although CBF-AML is categorized as favorable-risk AML, approximately 40% of patients show relapse. The t (8;21) and inv16 (q16q16) /t (16;16) (q16;q16) result in RUNX1-RUNX1T1 and CBFB-MYH11 fusion genes, respectively; however, the fusion proteins encoded by these genes alone are insufficient for the development of leukemia...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28792268/kit-mutations-correlate-with-adverse-survival-in-children-with-core-binding-factor-acute-myeloid-leukemia
#2
Xi Chen, Hu Dou, Xingjuan Wang, Yi Huang, Ling Lu, Junqing Bin, Yongchun Su, Lin Zou, Jie Yu, Liming Bao
The prevalence and clinical relevance of KIT mutations in childhood core-binding factor (CBF) acute myeloid leukemia (AML) have not been well characterized. In this study, a total of 212 children with de novo AML were enrolled from a Chinese population and 50 (23.5%) of the patients were deemed CBF-AML. KIT mutations were identified in 30% of the CBF-AML cohort. The KIT mutations were clustered in exon 17 and exon 8, and KIT mutations in exons 8 and 17 were correlated with a shorter overall survival (OS) (5-year OS: 30...
August 9, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28762080/d816-mutation-of-the-kit-gene-in-core-binding-factor-acute-myeloid-leukemia-is-associated-with-poorer-prognosis-than-other-kit-gene-mutations
#3
Shunsuke Yui, Saiko Kurosawa, Hiroki Yamaguchi, Heiwa Kanamori, Toshimitsu Ueki, Nobuhiko Uoshima, Ishikazu Mizuno, Katsuhiro Shono, Kensuke Usuki, Shigeru Chiba, Yukinori Nakamura, Masamitsu Yanada, Junya Kanda, Kenji Tajika, Seiji Gomi, Keiko Fukunaga, Satoshi Wakita, Takeshi Ryotokuji, Takahiro Fukuda, Koiti Inokuchi
The clinical impact of KIT mutations in core binding factor acute myeloid leukemia (CBF-AML) is still unclear. In the present study, we analyzed the prognostic significance of each KIT mutation (D816, N822K, and other mutations) in Japanese patients with CBF-AML. We retrospectively analyzed 136 cases of CBF-AML that had gone into complete remission (CR). KIT mutations were found in 61 (45%) of the patients with CBF-AML. D816, N822K, D816 and N822K, and other mutations of the KIT gene were detected in 29 cases (21%), 20 cases (15%), 7 cases (5%), and 5 cases (4%), respectively...
July 31, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28654205/driving-toward-precision-medicine-for-acute-leukemias-are-we-there-yet
#4
REVIEW
Clement Chung, Hilary Ma
Despite recent progress in the understanding of the molecular basis of acute leukemias, treatment options for these diseases have not changed significantly over the last few decades. We present a nonexhaustive summary of the current cytogenetic and molecular changes associated with acute leukemias in disease prognostication and potential targeted therapies. An emerging paradigm is that many genetic or molecular alterations target similar signal transduction, transcriptional, and epigenetic pathways. Some of these targets may be used as predictive biomarkers for the development of novel targeted therapies that depart significantly from conventional chemotherapy, the current mainstay for the treatment of acute leukemias...
September 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28618016/abcg2-and-cd200-define-patients-at-high-risk-of-relapse-in-eln-favorable-subgroup-of-aml
#5
Mario Tiribelli, Antonella Geromin, Margherita Cavallin, Sara Di Giusto, Erica Simeone, Renato Fanin, Daniela Damiani
OBJECTIVE: Overexpression of ABCG2 and CD200 has been independently associated with poor outcome in acute myeloid leukemia (AML). However, no data are available on the role of these two factors in patients with core-binding factor (CBF)-positive or FLT3-negative/NPM1-mutated cytogenetically normal (CN) AML. METHODS: We analyzed 65 adult AML patients with CBF+ (n=16) or FLT3-/NPM1+ CN (n=49), evaluating clinical and biological factors associated with complete remission attainment, leukemia-free survival (LFS) and overall survival (OS)...
September 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28506695/d816v-mutation-in-the-kit-gene-activation-loop-has-greater-cell-proliferative-and-anti-apoptotic-ability-than-n822k-mutation-in-core-binding-factor-acute-myeloid-leukemia
#6
Ikuko Omori, Hiroki Yamaguchi, Koichi Miyake, Noriko Miyake, Tomoaki Kitano, Koiti Inokuchi
In core-binding factor acute myeloid leukemia (CBF-AML), there have been conflicting reports regarding the status as an unfavorable prognostic factor of mutation in the KIT gene, the significance of which remains unclear. We previously reported that prognoses differ between the KIT D816V and N822K mutations. In the present study, we compared in vitro the cell-proliferative and anti-apoptotic ability of D816V and N822K. We transduced these KIT mutations into the interleukin-3-dependent cell line TF-1 (TF-1 KIT(D816V), TF-1 KIT(N822K))...
August 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28494506/minimal-residual-disease-eradication-with-epigenetic-therapy-in-core-binding-factor-acute-myeloid-leukemia
#7
Brittany Knick Ragon, Naval Daver, Guillermo Garcia-Manero, Farhad Ravandi, Jorge Cortes, Tapan Kadia, Betul Oran, Maro Ohanian, Alessandra Ferrajoli, Naveen Pemmaraju, Hagop M Kantarjian, Gautam Borthakur
Recurrent translocations, t(8;21) or inv(16), in core binding factor acute myeloid leukemia (CBF-AML) are amenable to monitoring for minimal residual disease (MRD) with reverse transcriptase polymerase chain reaction (RTPCR). Despite a favorable prognosis, disease relapse remains the single cause of treatment failure in CBF-AML. Fusion products of these translocations recruit epigenetic silencing complexes resulting in hematopoietic maturation arrest. We hypothesized that maintenance therapy with hypomethylating agents (HMA), including decitabine (DAC) and azacitidine (AZA) after induction/consolidation, can be used for MRD elimination to ultimately prolong relapse free survival...
September 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28299658/clinical-relevance-of-runx1-and-cbfb-alterations-in-acute-myeloid-leukemia-and-other-hematological-disorders
#8
Klaus H Metzeler, Clara D Bloomfield
The translocation t(8;21), leading to a fusion between the RUNX1 gene and the RUNX1T1 locus, was the first chromosomal translocation identified in cancer. Since the first description of this balanced rearrangement in a patient with acute myeloid leukemia (AML) in 1973, RUNX1 translocations and point mutations have been found in various myeloid and lymphoid neoplasms. In this chapter, we summarize the currently available data on the clinical relevance of core binding factor gene alterations in hematological disorders...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28119329/marker-chromosomes-can-arise-from-chromothripsis-and-predict-adverse-prognosis-in-acute-myeloid-leukemia
#9
RANDOMIZED CONTROLLED TRIAL
Tilmann Bochtler, Martin Granzow, Friedrich Stölzel, Christina Kunz, Brigitte Mohr, Mutlu Kartal-Kaess, Katrin Hinderhofer, Christoph E Heilig, Michael Kramer, Christian Thiede, Volker Endris, Martina Kirchner, Albrecht Stenzinger, Axel Benner, Martin Bornhäuser, Gerhard Ehninger, Anthony D Ho, Anna Jauch, Alwin Krämer
Metaphase karyotyping is an established diagnostic standard in acute myeloid leukemia (AML) for risk stratification. One of the cytogenetic findings in AML is structurally highly abnormal marker chromosomes. In this study, we have assessed frequency, cytogenetic characteristics, prognostic impact, and underlying biological origin of marker chromosomes. Given their inherent gross structural chromosomal damage, we speculated that they may arise from chromothripsis, a recently described phenomenon of chromosome fragmentation in a single catastrophic event...
March 9, 2017: Blood
https://www.readbyqxmd.com/read/28089879/clinical-outcome-of-autologous-hematopoietic-cell-transplantation-in-adult-patients-with-acute-myeloid-leukemia-who-may-benefit-from-autologous-hematopoietic-cell-transplantation
#10
Jae-Ho Yoon, Hee-Je Kim, Sung-Soo Park, Young-Woo Jeon, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min
The role of autologous hematopoietic cell transplantation (auto-HCT) for postremission therapy of acute myeloid leukemia is yet to be elucidated. We retrospectively analyzed 240 patients treated with auto-HCT in first remission. All patients were treated with standard induction chemotherapy, and CD34(+) stem cells were collected at each cycle of consolidation. Stem cells were infused after total body irradiation (1200 cGy), cytarabine (9 g/m(2)), and melphalan (100 mg/m(2)). Estimated 5-year overall survival, disease-free survival (DFS), cumulative incidence of relapse (CIR), and nonrelapse mortality were 58...
April 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27843138/mutations-in-the-ccnd1-and-ccnd2-genes-are-frequent-events-in-adult-patients-with-t-8-21-q22-q22-acute-myeloid-leukemia
#11
A-K Eisfeld, J Kohlschmidt, S Schwind, D Nicolet, J S Blachly, S Orwick, C Shah, M Bainazar, K W Kroll, C J Walker, A J Carroll, B L Powell, R M Stone, J E Kolitz, M R Baer, A de la Chapelle, K Mrózek, J C Byrd, C D Bloomfield
Core-binding factor acute myeloid leukemia (CBF-AML) is defined by the presence of either t(8;21)(q22;q22)/RUNX1-RUNX1T1 or inv(16)(p13.1q22)/t(16;16)(p13.1;q22)/CBFB-MYH11. The resulting fusion genes require a 'second hit' to initiate leukemogenesis. Mutation assessment of 177 adults with CBF-AML, including 68 with t(8;21) and 109 with inv(16)/t(16;16), identified not only mutations well known in CBF-AML but also mutations in the CCND1 and CCND2 genes, which represent novel frequent molecular alterations in AML with t(8;21)...
June 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27798625/the-genomic-landscape-of-core-binding-factor-acute-myeloid-leukemias
#12
Zachary J Faber, Xiang Chen, Amanda Larson Gedman, Kristy Boggs, Jinjun Cheng, Jing Ma, Ina Radtke, Jyh-Rong Chao, Michael P Walsh, Guangchun Song, Anna K Andersson, Jinjun Dang, Li Dong, Yu Liu, Robert Huether, Zhongling Cai, Heather Mulder, Gang Wu, Michael Edmonson, Michael Rusch, Chunxu Qu, Yongjin Li, Bhavin Vadodaria, Jianmin Wang, Erin Hedlund, Xueyuan Cao, Donald Yergeau, Joy Nakitandwe, Stanley B Pounds, Sheila Shurtleff, Robert S Fulton, Lucinda L Fulton, John Easton, Evan Parganas, Ching-Hon Pui, Jeffrey E Rubnitz, Li Ding, Elaine R Mardis, Richard K Wilson, Tanja A Gruber, Charles G Mullighan, Richard F Schlenk, Peter Paschka, Konstanze Döhner, Hartmut Döhner, Lars Bullinger, Jinghui Zhang, Jeffery M Klco, James R Downing
Acute myeloid leukemia (AML) comprises a heterogeneous group of leukemias frequently defined by recurrent cytogenetic abnormalities, including rearrangements involving the core-binding factor (CBF) transcriptional complex. To better understand the genomic landscape of CBF-AMLs, we analyzed both pediatric (n = 87) and adult (n = 78) samples, including cases with RUNX1-RUNX1T1 (n = 85) or CBFB-MYH11 (n = 80) rearrangements, by whole-genome or whole-exome sequencing. In addition to known mutations in the Ras pathway, we identified recurrent stabilizing mutations in CCND2, suggesting a previously unappreciated cooperating pathway in CBF-AML...
December 2016: Nature Genetics
https://www.readbyqxmd.com/read/27795558/expression-of-cd33-is-a-predictive-factor-for-effect-of-gemtuzumab-ozogamicin-at-different-doses-in-adult-acute-myeloid-leukaemia
#13
RANDOMIZED CONTROLLED TRIAL
N Khan, R K Hills, P Virgo, S Couzens, N Clark, A Gilkes, P Richardson, S Knapper, D Grimwade, N H Russell, A K Burnett, S D Freeman
It remains unclear in adult acute myeloid leukaemia (AML) whether leukaemic expression of CD33, the target antigen for gemtuzumab ozogamicin (GO), adds prognostic information on GO effectiveness at different doses. CD33 expression quantified in 1583 patients recruited to UK-NCRI-AML17 (younger adults) and UK-NCRI-AML16 (older adults) trials was correlated with clinical outcomes and benefit from GO including a dose randomisation. CD33 expression associated with genetic subgroups, including lower levels in both adverse karyotype and core-binding factor (CBF)-AML, but was not independently prognostic...
May 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27643573/karyotype-plus-npm1-mutation-status-defines-a-group-of-elderly-patients-with-aml-%C3%A2-60-years-who-benefit-from-intensive-post-induction-consolidation-therapy
#14
Wolfgang R Sperr, Otto Zach, Iris Pöll, Susanne Herndlhofer, Paul Knoebl, Ansgar Weltermann, Berthold Streubel, Ulrich Jaeger, Michael Kundi, Peter Valent
Although it is generally appreciated that a subset of elderly patients with acute myeloid leukemia (AML) may benefit from intensive consolidation, little is known about variables predicting such benefit. We analyzed 192 consecutive patients with de novo AML aged ≥60 years who were treated with intensive chemotherapy. About 115 patients (60%) achieved complete hematologic remission (CR). Among several parameters, the karyotype was the only independent variable predicting CR (P < 0.05). About 92% (105/115) of the CR-patients received up to four consolidation cycles of intermediate dose ARA-C...
December 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27613372/prognostic-importance-of-c-kit-mutations-in-core-binding-factor-acute-myeloid-leukemia-a-systematic-review
#15
REVIEW
Hossein Ayatollahi, Arezoo Shajiei, Mohammad Hadi Sadeghian, Maryam Sheikhi, Ehsan Yazdandoust, Masumeh Ghazanfarpour, Seyyede Fatemeh Shams, Sepideh Shakeri
OBJECTIVE/BACKGROUND: Acute myeloid leukemia (AML) is defined as leukemic blast reproduction in bone marrow. Chromosomal abnormalities form different subgroups with joint clinical specifications and results. t(8;21)(q22;q22) and inv(16)(p13;q22) form core binding factor-AML (CBF-AML). c-kit mutation activation occurs in 12.8-46.1% of adults with CBF leukemia. These mutations occur in 20-25% of t(8;21) and 30% of inv(16) cases. METHODS: In this systematic review, we searched different databases, including PubMed, Scopus, and Embase...
March 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/27597292/predictive-value-of-molecular-remissions-postconsolidation-chemotherapy-in-patients-with-core-binding-factor-acute-myeloid-leukemia-cbf-aml-a-single-center-analysis
#16
Uday Deotare, Marwan Shaheen, Joseph M Brandwein, Bethany Pitcher, Suzanne Kamel-Reid, Karen W L Yee, Aaron Schimmer, Mark D Minden, Vikas Gupta, Andre C Schuh
We analyzed the outcome of 80 sequential patients with core binding factor acute myeloid leukemia and evaluated the influence of molecular monitoring by quantitative reverse transcriptase polymerase chain reaction. With a median follow-up of 5 years, the estimated 5-year relapse-free survival and overall survival were 58% and 66%, respectively. Patients who were in molecular remission at the completion of consolidation chemotherapy had a 21% risk of relapse, while the relapse risk for those in molecular remission at the end of 2 years was 5...
September 6, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27512117/bpr1j373-an-oral-multiple-tyrosine-kinase-inhibitor-targets-c-kit-for-the-treatment-of-c-kit-driven-myeloid-leukemia
#17
Li-Tzong Chen, Chiung-Tong Chen, Weir-Torn Jiaang, Tsai-Yun Chen, Joseph H Butterfield, Neng-Yao Shih, John Tsu-An Hsu, Hui-You Lin, Sheng-Fung Lin, Hui-Jen Tsai
Acute myelogenous leukemia (AML) carrying t(8;21)(q22;q22) or inv(16)/t(16;16)(p13;q22) is classified as core binding factor (CBF)-AML and accounts for approximately 15% of AML. c-KIT mutation can be detected in 17%∼46% of CBF-AML and is associated with poor prognosis. c-KIT mutation is a crucial hit and cooperates with AML1-ETO resulting from t(8;21)(q22;q22) to cause overt AML. Tyrosine kinase inhibitors (TKI) targeting c-KIT, such as imatinib, has been used successfully to treat c-KIT driven gastrointestinal stromal tumors...
October 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27298396/comparison-of-multiparameter-flow-cytometry-immunophenotypic-analysis-and-quantitative-rt-pcr-for-the-detection-of-minimal-residual-disease-of-core-binding-factor-acute-myeloid-leukemia
#18
COMPARATIVE STUDY
Juan Ouyang, Maitrayee Goswami, Jie Peng, Zhuang Zuo, Naval Daver, Gautam Borthakur, Guilin Tang, L Jeffrey Medeiros, Jeffrey L Jorgensen, Farhad Ravandi, Sa A Wang
OBJECTIVES: To examine the value of minimal residual disease (MRD) by multiparameter flow cytometry (MFC) in core binding factor (CBF) acute myeloid leukemia (AML). METHODS: We studied 42 patients with t(8;21)(q22;q22)/RUNX1-RUNX1T1 and 51 with inv(16)(p13.1q22)/CBFB-MYH11 Tandem MRD analyses by MFC and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were performed in 281 bone marrow (BM) samples. RESULTS: Grouping qRT-PCR levels as ≤0...
June 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/27297971/bcr-abl-positive-acute-myeloid-leukemia-a-new-entity-analysis-of-clinical-and-molecular-features
#19
Nina Rosa Neuendorff, Thomas Burmeister, Bernd Dörken, Jörg Westermann
BCR-ABL-positive acute myeloid leukemia (AML) is a rare subtype of AML that is now included as a provisional entity in the 2016 revised WHO classification of myeloid malignancies. Since a clear distinction between de novo BCR-ABL+ AML and chronic myeloid leukemia (CML) blast crisis is challenging in many cases, the existence of de novo BCR-ABL+ AML has been a matter of debate for a long time. However, there is increasing evidence suggesting that BCR-ABL+ AML is in fact a distinct subgroup of AML. In this study, we analyzed all published cases since 1975 as well as cases from our institution in order to present common clinical and molecular features of this rare disease...
August 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27207321/beyond-kit-in-cbf-aml-chromatin-and-cohesin
#20
Rachel E Rau
No abstract text is available yet for this article.
May 19, 2016: Blood
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