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https://www.readbyqxmd.com/read/28102729/chronic-myelomonocytic-leukemia-with-double-mutations-in-dnmt3a-and-flt3-itd-treated-with-decitabine-and-sorafenib
#1
Jia Gu, Zhiqiong Wang, Min Xiao, Xia Mao, Li Zhu, Ying Wang, Wei Huang
Chronic myelomonocytic leukemia (CMML) is a heterogeneous neoplastic hematologic disorder with worse overall survival. Half of CMML have mutations, but case with concomitant mutations of DNA methyltransferase 3A (DNMT3A) and Internal tandem duplications of the juxtamembrane domain of FLT3 (FLT3-ITD) in CMML was not reported before. We reported a 51-year-old man who had CMML with concomitant mutations in DNMT3A and FLT3-ITD.The patient received decitabine and sorafenib combined treatment. In this report, we reviewed DNMT3A mutation and FLT3 mutation, and we reviewed treatment of decitabine and sorafenib...
January 19, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28101583/integrated-analysis-of-microrna-and-transcription-factor-reveals-important-regulators-and-regulatory-motifs-in-adult-b-cell-acute-lymphoblastic-leukemia
#2
Xiao-Cong Lin, Xin-Guang Liu, Yu-Ming Zhang, Ning Li, Zhi-Gang Yang, Wei-Yu Fu, Liu-Bo Lan, Hai-Tao Zhang, Yong Dai
B-cell acute lymphoblastic leukemia (B‑ALL) is an aggressive hematological malignancy and a leading cause of cancer-related mortality in children and young adults. The molecular mechanisms involved in the regulation of its gene expression has yet to be fully elucidated. In the present study, we performed large scale expression profiling of microRNA (miRNA) and transcription factor (TF) by Illumina deep‑sequencing and TF array technology, respectively, and identified 291 differentially expressed miRNAs and 201 differentially expressed TFs in adult B‑ALL samples relative to their controls...
February 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28100593/clinical-implications-of-dnmt3a-mutations-in-a-southeast-asian-cohort-of-acute-myeloid-leukaemia-patients
#3
Marcus Tan, Isaac K S Ng, Zhaojin Chen, Kenneth Ban, Christopher Ng, Lily Chiu, Elaine Seah, Mingxuan Lin, Bee Choo Tai, Benedict Yan, Chin Hin Ng, Wee-Joo Chng
AIMS: In recent years, genomic technologies have enabled the identification of mutations in acute myeloid leukaemia (AML). DNMT3A is a recurrently mutated epigenetic modifier gene in AML. To date, the prognostic significance of DNMT3A mutations has not been studied in a Southeast Asian AML population. We sought to investigate the clinical implications of DNMT3A mutations in a Southeast Asian cohort of AML patients. METHODS: DNMT3A mutations were identified using a targeted next-generation sequencing panel in 157 AML patients...
January 18, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28091414/acute-myeloid-leukemia-advancements-in-diagnosis-and-treatment
#4
REVIEW
Meng-Ge Yu, Hu-Yong Zheng
OBJECTIVE: Leukemia is the most common pediatric malignancy and a major cause of morbidity and mortality in children. Among all subtypes, a lack of consensus exists regarding the diagnosis and treatment of acute myeloid leukemia (AML). Patient survival rates have remained modest for the past three decades in AML. Recently, targeted therapy has emerged as a promising treatment. DATA SOURCES: We searched the PubMed database for recently published research papers on diagnostic development, target therapy, and other novel therapies of AML...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28090796/impact-of-c-rel-inhibition-of-cord-blood-derived-b-t-and-nk-cells
#5
Shirin Fallahi, Seyede Momeneh Mohammadi, Hamid Tayefi Nasrabadi, Alireza Alihemmati, Naser Samadi, Sanaz Gholami, Dariush Shanehbandi, Hojjatollah Nozad Charoudeh
The c-Rel transcription factor is a unique member of the nuclear factor (NF)-κB family that has a role in curtailing the proliferation, differentiation, cytokine production, and overall activity of B- and T-cells. In addition, c-Rel is a key regulator of apoptosis in that it influences the expression of anti-apoptotic genes such as Bcl-2 and Bcl-xL; conversely, inhibition of c-Rel increases cell apoptosis. To better understand the relationship between c-Rel expression and effects on B- and T-cell expansion, the current study evaluated c-Rel expression in cord blood mononuclear cells...
January 16, 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28089916/stable-curcumin-loaded-polymeric-micellar-formulation-for-enhancing-cellular-uptake-and-cytotoxicity-to-flt3-overexpressing-eol-1-leukemic-cells
#6
Singkome Tima, Songyot Anuchapreeda, Chadarat Ampasavate, Cory Berkland, Siriporn Okonogi
The present study aims to develop a stable polymeric micellar formulation of curcumin (CM) with improved solubility and stability, and that is suitable for clinical applications in leukemia patients. CM-loaded polymeric micelles (CM-micelles) were prepared using poloxamers. The chemical structure of the polymers influenced micellar properties. The best formulation of CM-micelles, namely CM-P407, was obtained from poloxamer 407 at drug to polymer ratio of 1:30 and rehydrated with phosphate buffer solution pH 7...
January 12, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28089879/clinical-outcome-of-autologous-hematopoietic-cell-transplantation-hct-in-adult-patients-with-acute-myeloid-leukemia-who-may-benefit-from-autologous-hct
#7
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 (auto)-hematopoietic cell transplantation (HCT) for post-remission therapy of acute myeloid leukemia (AML) 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 following TBI (1200cGy), cytarabine (9g/BSA), and melphalan (100mg/BSA). Estimated 5-year overall survival, disease free survival (DFS), cumulative incidence of relapse (CIR), and non-relapse mortality was 58...
January 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28088962/-efficacy-and-safety-of-sorafenib-as-monotherapy-to-flt3-itd-positive-acute-myeloid-leukemia
#8
J S Jia, H H Zhu, H X Fu, L Z Gong, J Kong, X J Huang, H Jiang
Objective: To explore the efficacy and safety of Sorafenib as monotherapy to FLT3 positive acute myeloid leukemia (AML). Methods: From April 2014 to December 2015, fourteen AML patients with FLT3 positive, 7 males and 7 females with a median age of 42 (range: 14-81) years old, were enrolled in this study. Of the 14 cases, 4 were de novo cases, 9 refractory cases and 1 relapsed case, including 78.6% patients with severe complications and 57.1% patients with KPS score less than 60 [the median KPS score was 45 (20-70) ]...
December 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28088961/-the-clinical-and-prognostic-significance-of-acute-myeloid-leukemia-with-flt3-itd
#9
D Lin, H Wei, Y Wang, C L Zhou, B C Liu, K Q Liu, B F Gong, S N Wei, G J Zhang, Y T Liu, X Y Gong, S W Qiu, Y C Mi, J X Wang
Objective: To investigate the clinical significance and prognosis factors of acute myeloid leukemia (AML) with FLT3 mutation-internal tandem duplication (FLT3-ITD) and provide more evidence for prognosis evaluation in AML with FLT3-ITD. Methods: The clinical characteristics and outcomes of 98 AML with FLT3-ITD were analyzed. Results: In patients with FLT3-ITD positive AML, the median of WBC and peripheral blood blast at initial diagnosis were 58.2 (0.3-461.8) ×10(9)/L and 42.2 (0-397.1) ×10(9)/L, respectively...
December 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28077790/flt3-activating-mutations-display-differential-sensitivity-to-multiple-tyrosine-kinase-inhibitors
#10
Bao Nguyen, Allen B Williams, David J Young, Hayley Ma, Li Li, Mark Levis, Patrick Brown, Donald Small
Fms-like tyrosine kinase-3 (FLT3) is a receptor tyrosine kinase that normally functions in hematopoietic cell survival, proliferation and differentiation. Constitutively activating mutations of FLT3 map predominately to the juxtamembrane domain (internal tandem duplications; ITD) or the activation loop (AL) of the kinase domain and are detected in about 1/3 of de novo acute myeloid leukemia (AML) patients. Small molecule tyrosine kinase inhibitors (TKI) effectively target FLT3/ITD mutations, but some activating mutations, particularly those on the AL, are relatively resistant to many FLT3 TKI...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28077417/aid-is-a-key-regulator-of-myeloid-erythroid-differentiation-and-dna-methylation-in-hematopoietic-stem-progenitor-cells
#11
Hiroyoshi Kunimoto, Anna Sophia McKenney, Cem Meydan, Kaitlyn Shank, Abbas Nazir, Franck Rapaport, Benjamin Durham, Francine E Garrett-Bakelman, Elodie Pronier, Alan H Shih, Ari Melnick, Jayanta Chaudhuri, Ross L Levine
Recent studies have reported activation-induced cytidine deaminase (AID) and ten-eleven-translocation (TET) family members regulate active DNA demethylation. Genetic alterations of TET2 occur in myeloid malignancies and hematopoietic specific loss of Tet2 induces aberrant hematopoietic stem cell (HSC) self-renewal/differentiation, implicating TET2 as a master regulator of normal and malignant hematopoiesis. Despite the functional link between AID and TET in epigenetic gene regulation, the role of AID loss in hematopoiesis and myeloid transformation remains to be investigated...
January 11, 2017: Blood
https://www.readbyqxmd.com/read/28076826/identification-of-new-pyrrolo-2-3-d-pyrimidines-as-src-tyrosine-kinase-inhibitors-in%C3%A2-vitro-active-against-glioblastoma
#12
Francesca Musumeci, Anna Lucia Fallacara, Chiara Brullo, Giancarlo Grossi, Lorenzo Botta, Pierpaolo Calandro, Mario Chiariello, Miroslava Kissova, Emmanuele Crespan, Giovanni Maga, Silvia Schenone
In the last few years, several pyrrolo-pyrimidine derivatives have been either approved by the US FDA and in other countries for the treatment of different diseases or are currently in phase I/II clinical trials. Herein we present the synthesis and the characterization of a novel series of pyrrolo[2,3-d]pyrimidines, compounds 8a-j, and their activity against Glioblastoma multiforme (GBM). Docking studies and MM-GBSA analysis revealed the ability of such compounds to efficiently interact with the ATP binding site of Src...
December 19, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28070990/a-targeted-next-generation-sequencing-in-the-molecular-risk-stratification-of-adult-acute-myeloid-leukemia-implications-for-clinical-practice
#13
Po-Han Lin, Huei-Ying Li, Sheng-Chih Fan, Tzu-Hang Yuan, Ming Chen, Yu-Hua Hsu, Yu-Hsuan Yang, Long-Yuan Li, Su-Peng Yeh, Li-Yuan Bai, Yu-Min Liao, Chen-Yuan Lin, Ching-Yun Hsieh, Ching-Chan Lin, Che-Hung Lin, Ming-Yu Lien, Tzu-Ting Chen, Yen-Hsuan Ni, Chang-Fang Chiu
Conventional cytogenetics can categorize patients with acute myeloid leukemia (AML) into favorable, intermediate, and unfavorable-risk groups; however, patients with intermediate-risk cytogenetics represent the major population with variable outcomes. Because molecular profiling can assist with AML prognosis and next-generation sequencing allows simultaneous sequencing of many target genes, we analyzed 260 genes in 112 patients with de novo AML who received standard treatment. Multivariate analysis showed that karyotypes and mutation status of TET2, PHF6, KIT, and NPM1(mutation) /FLT3- internal tandem duplication (ITD)(negative) were independent prognostic factors for the entire cohort...
January 10, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28061447/the-combination-effect-of-homoharringtonine-and-ibrutinib-on-flt3-itd-mutant-acute-myeloid-leukemia
#14
Xia Li, Xiufeng Yin, Huafeng Wang, Jiansong Huang, Mengxia Yu, Zhixin Ma, Chenying Li, Yile Zhou, Xiao Yan, ShuJuan Huang, Jie Jin
Acute myeloid leukemia (AML) is a highly heterogeneous disease and internal tandem duplication mutation in FMS-like tyrosine-kinase-3 (FLT3-ITD) has a negative impact on outcome. Finding effective treatment regimens is desperately needed. In this study, we explored the inhibitory effect and mechanism of homoharringtonine (HHT) in combination with ibrutinib on FLT3-ITD mutant AML cells. Consequently, we observed a synergistic inhibitory effect when ibrutinib was combined with HHT to inhibit cell proliferation, induce apoptosis and arrest cell cycle at G0/G1 phase in MV4-11 and MOLM-13 leukemia cells...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28058491/evaluating-the-impact-of-genetic-and-epigenetic-aberrations-on-survival-and-response-in-acute-myeloid-leukemia-patients-receiving-epigenetic-therapy
#15
Jan K Hiller, Claudia Schmoor, Verena I Gaidzik, Charlotte Schmidt-Salzmann, Arzu Yalcin, Mahmoud Abdelkarim, Nadja Blagitko-Dorfs, Konstanze Döhner, Lars Bullinger, Justus Duyster, Michael Lübbert, Björn Hackanson
Treatment with hypomethylating agents such as decitabine, which results in overall response rates of up to 50%, has become standard of care in older patients with acute myeloid leukemia (AML) who are not candidates for intensive chemotherapy. However, there still exists a lack of prognostic and predictive molecular biomarkers that enable selection of patients who are likely to benefit from epigenetic therapy. Here, we investigated distinct genetic (FLT3-ITD, NPM1, DNMT3A) and epigenetic (estrogen receptor alpha (ERα), C/EBPα, and OLIG2) aberrations in 87 AML patients from the recently published phase II decitabine trial (AML00331) to identify potential biomarkers for patients receiving hypomethylating therapy...
January 5, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28056203/postinduction-minimal-residual-disease-predicts-outcome-and-benefit-from-allogeneic-stem-cell-transplantation-in-acute-myeloid-leukemia-with-npm1-mutation-a-study-by-the-acute-leukemia-french-association-group
#16
Marie Balsat, Aline Renneville, Xavier Thomas, Stéphane de Botton, Denis Caillot, Alice Marceau, Emilie Lemasle, Jean-Pierre Marolleau, Olivier Nibourel, Céline Berthon, Emmanuel Raffoux, Arnaud Pigneux, Céline Rodriguez, Norbert Vey, Jean-Michel Cayuela, Sandrine Hayette, Thorsten Braun, Marie Magdeleine Coudé, Christine Terre, Karine Celli-Lebras, Hervé Dombret, Claude Preudhomme, Nicolas Boissel
Purpose This study assessed the prognostic impact of postinduction NPM1-mutated ( NPM1m) minimal residual disease (MRD) in young adult patients (age, 18 to 60 years) with acute myeloid leukemia, and addressed the question of whether NPM1m MRD may be used as a predictive factor of allogeneic stem cell transplantation (ASCT) benefit. Patients and Methods Among 229 patients with NPM1m who were treated in the Acute Leukemia French Association 0702 (ALFA-0702) trial, MRD evaluation was available in 152 patients in first remission...
January 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28052408/relapse-risk-and-survival-in-patients-with-flt3-acute-myeloid-leukemia-undergoing-stem-cell-transplantation
#17
Sameh Gaballa, Rima Saliba, Betul Oran, Jonathan E Brammer, Julianne Chen, Gabriela Rondon, Amin M Alousi, Partow Kebriaei, David Marin, Uday R Popat, Borje S Andersson, Elizabeth J Shpall, Elias Jabbour, Naval Daver, Michael Andreeff, Farhad Ravandi, Jorge Cortes, Keyur Patel, Richard E Champlin, Stefan O Ciurea
In patients with AML with FMS-like tyrosine kinase 3 (FLT3) mutations, the significance of minimal residual disease (MRD) detected by PCR before allogeneic stem cell transplantation (SCT) on outcomes after transplant remains unclear. We identified 200 patients with FLT3-AML who underwent SCT at our institution. Disease status at transplant was: first or second complete remission (CR1/CR2, n=119), high-risk CR (third or subsequent CR, marrow hypoplasia, or incomplete count recovery) (CR-HR, n=31), and morphological evidence of active disease (AD, n=50)...
January 4, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28052366/impact-of-fab-classification-on-predicting-outcome-in-acute-myeloid-leukemia-not-otherwise-specified-patients-undergoing-allogeneic-stem-cell-transplantation-in-cr1-an-analysis-of-1690-patients-from-the-acute-leukemia-working-party-of-ebmt
#18
Jonathan Canaani, Eric Beohou, Myriam Labopin, Gerard Socié, Anne Huynh, Liisa Volin, Jan Cornelissen, Noel Milpied, Tobias Gedde-Dahl, Eric Deconinck, Nathalie Fegueux, Didier Blaise, Mohamad Mohty, Arnon Nagler
The French, American, and British (FAB) classification system for acute myeloid leukemia (AML) is extensively used and is incorporated into the AML, not otherwise specified (NOS) category in the 2016 WHO edition of myeloid neoplasm classification. While recent data proposes that FAB classification does not provide additional prognostic information for patients for whom NPM1 status is available, it is unknown whether FAB still retains a current prognostic role in predicting outcome of AML patients undergoing allogeneic stem cell transplantation...
January 4, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28049642/therapeutic-value-of-clofarabine-in-younger-and-middle-aged-18-65-yrs-adults-with-newly-diagnosed-aml
#19
Bob Löwenberg, Thomas Pabst, Johan Maertens, Yvette van Norden, Bart J Biemond, Harry C Schouten, Olivier Spertini, Edo Vellenga, Carlos Graux, Violaine Havelange, Georgine E de Greef, Okke de Weerdt, Marie-Cecile J C Legdeur, Juergen Kuball, Marinus van Marwijk Kooy, Bjorn T Gjertsen, Mojca Jongen-Lavrencic, Arjan A van de Loosdrecht, Daniëlle van Lammeren-Venema, Beata Hodossy, Dimitri A Breems, Yves Chalandon, Jakob Passweg, Peter J M Valk, Markus G Manz, Gert J Ossenkoppele
Clofarabine has demonstrated antileukemic activity in acute myeloid leukemia (AML) but has yet to be critically evaluated in younger adults in the frontline with standard chemotherapy. We compared two induction regimens in newly diagnosed patients aged 18-65 with AML/high risk MDS, i.e., idarubicine-cytarabine (cycle I) and amsacrine-cytarabine (cycle II) without or with clofarabine (10 mg/m(2) on days 1-5 of each of both cycles). Consolidation involved chemotherapy with or without hematopoietic stem cell transplantation...
January 3, 2017: Blood
https://www.readbyqxmd.com/read/28043794/synthetic-strategy-for-increasing-solubility-of-potential-flt3-inhibitor-thieno-2-3-d-pyrimidine-derivatives-through-structural-modifications-at-the-c2-and-c6-positions
#20
Changmok Oh, Hyuntae Kim, Jong Soon Kang, Jieun Yun, Jaejun Sim, Hwan-Mook Kim, Gyoonhee Han
Acute myeloid leukemia (AML) is a clonal disorder of hematopoietic progenitor cell. In AML, a mutation in FLT3 is commonly occurs and is associated with poor prognosis. We have previously reported that thieno[2,3-d]pyrimidine derivative compound 1 exhibited better antiproliferative activity against MV4-11 cells which harbor mutant FLT3 than AC220, which is a well-known FLT3 inhibitor, and has good microsomal stability. However, compound 1 had poor solubility. We then carried out further structural modification at the C2 and the C6 positions of thieno[2,3-d]pyrimidine scaffold...
December 23, 2016: Bioorganic & Medicinal Chemistry Letters
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