keyword
MENU ▼
Read by QxMD icon Read
search

Flt3

keyword
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#1
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29037944/identification-of-pyrrolo-2-3-d-pyrimidines-as-potent-hck-and-flt3-itd-dual-inhibitors
#2
Yasuko Koda, Ko Kikuzato, Junko Mikuni, Akiko Tanaka, Hitomi Yuki, Teruki Honma, Yuri Tomabechi, Mutsuko Kukimoto-Niino, Mikako Shirouzu, Fumiyuki Shirai, Hiroo Koyama
A series of novel pyrrolo[2,3-d]pyrimidines were synthesized by introducing 15 different amino acids to 7-cyclohexyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine-4-amine. Compounds with potent activities against HCK and FLT3-ITD were evaluated in viability studies with acute myeloid leukemia cell line MV4-11. Our structure activity relationship analyses lead to the identification of compound 31, which exhibited potent HCK and FLT3-ITD inhibition and activity against the MV4-11 cell line.
October 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29034366/a-phase-2-study-incorporating-sorafenib-into-the-chemotherapy-for-older-adults-with-flt3-mutated-acute-myeloid-leukemia-calgb-11001
#3
Geoffrey L Uy, Sumithra J Mandrekar, Kristina Laumann, Guido Marcucci, Weiqiang Zhao, Mark J Levis, Heidi D Klepin, Maria R Baer, Bayard L Powell, Peter Westervelt, Daniel J DeAngelo, Wendy Stock, Ben Sanford, William G Blum, Clara D Bloomfield, Richard M Stone, Richard A Larson
The Cancer and Leukemia Group B (CALGB), now part of the Alliance for Clinical Trials in Oncology, conducted a multicenter, single-arm, phase 2 study in patients ≥60 years with FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML). In this study, sorafenib was added to daunorubicin and cytarabine-based induction and consolidation chemotherapy and was also continued for 12 months of maintenance therapy. The primary end point of the study was overall survival (OS) at 1 year in the FLT3 internal tandem duplication (FLT3-ITD) cohort...
January 24, 2017: Blood Advances
https://www.readbyqxmd.com/read/29027108/prognostic-value-of-genetic-mutations-in-adolescent-and-young-adults-with-acute-myeloid-leukemia
#4
Yachiyo Kuwatsuka, Daisuke Tomizawa, Rika Kihara, Yasunobu Nagata, Norio Shiba, Yuka Iijima-Yamashita, Akira Shimada, Takao Deguchi, Hayato Miyachi, Akio Tawa, Takashi Taga, Akitoshi Kinoshita, Hideki Nakayama, Nobutaka Kiyokawa, Akiko Moriya Saito, Katsuyoshi Koh, Hiroaki Goto, Yoshiyuki Kosaka, Norio Asou, Shigeki Ohtake, Shuichi Miyawaki, Yasushi Miyazaki, Toru Sakura, Yukiyasu Ozawa, Noriko Usui, Heiwa Kanamori, Yoshikazu Ito, Kiyotoshi Imai, Youko Suehiro, Shinichi Kobayashi, Kunio Kitamura, Emiko Sakaida, Seishi Ogawa, Tomoki Naoe, Yasuhide Hayashi, Keizo Horibe, Atsushi Manabe, Shuki Mizutani, Souichi Adachi, Hitoshi Kiyoi
Clinical outcomes and the genetic background of acute myeloid leukemia (AML) in adolescent and young adults (AYAs) are known to differ in younger children and older adults. To clarify the impact of genetic mutations on clinical outcomes of AYAs with AML, we analyzed data from the JPLSG AML-05 and JALSG AML201 studies. AYAs aged 15-39 years (n = 103) were included. FLT3-ITD, KIT, CEBPA, NRAS, KRAS, WT1, MLL-PTD, and NPM1 mutations were analyzed. Overall survival (OS) of the AYAs was 61% and event-free survival was 38% at 3 years...
October 12, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29025582/a-novel-trip11-flt3-fusion-in-a-patient-with-a-myeloid-lymphoid-neoplasm-with-eosinophilia
#5
Alfred Chung, Yanli Hou, Robert S Ohgami, Ann Von Gehr, Dianna G Fisk, Krishna M Roskin, Xu Li, Linda Gojenola, Charles D Bangs, Daniel A Arber, Andrew Z Fire, Athena M Cherry, James L Zehnder, Jason Gotlib, Jason D Merker
FLT3 fusions are associated with myeloid and lymphoid neoplasms with eosinophilia. We describe a patient presenting with clinicopathologic features of both chronic eosinophilic leukemia, not otherwise specified (CEL, NOS) and systemic mastocytosis (SM). The bone marrow demonstrated a myeloproliferative neoplasm with eosinophilia and aggregates of atypical mast cells. Cytogenetic analysis revealed a t(13;14)(q12;q32), which was subsequently molecularly characterized as a novel TRIP11-FLT3 rearrangement. A KIT D816V mutation was also identified...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29017371/cytarabine-and-daunorubicin-for-the-treatment-of-acute-myeloid-leukemia
#6
Tracy Murphy, Karen Wl Yee
Acute myeloid leukemia (AML) is the most common acute forms of leukemia in adults. It has a poor long-term survival with a high relapse rate and at relapse, is commonly resistant to available therapies. The current combination of daunorubicin (DNR) for three days and cytarabine (Ara-C) as a continuous infusion for seven days, more commonly known as '3+7' has remained essentially unaltered over the last forty-four years and remains the standard induction regimen internationally. Areas covered: This paper will briefly review clinically important trials related to '3+7'...
October 11, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28990511/sunitinib-in-the-treatment-of-thyroid-cancer
#7
Ferrari Silvia Martinaa, Centanni Marco, Virili Camilla, Miccoli Mario, Ferrari Paola, Ruffilli Ilaria, Ragusa Francesca, Antonelli Alessandro, Fallahi Poupak
BACKGROUND: Sunitinib (SU11248) is an oral, small-molecule, multi-targeted tyrosine kinase inhibitor (TKI), that inhibits receptors for platelet-derived growth factor (PDGF-Rs) and vascular endothelial growth factor receptors (VEGFRs), c-KIT, fms-related tyrosine kinase 3 (FLT3) and RET. The concurrent inhibition of these pathways reduces tumor vascularization and causes cancer cell apoptosis, inducing a tumor shrinkage. Sunitinib is approved for the treatment of imatinib-resistant gastrointestinal stromal tumor (GIST), renal carcinoma, and pancreatic neuroendocrine tumors...
October 6, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28989589/aberrant-methylation-of-apaf-1-gene-in-acute-myeloid-leukemia-patients
#8
Shahrbano Rostami, Fatemeh Nadali, Reza Alibakhshi, Farhad Zaker, Nahid Nasiri, Mehrdad Payandeh, Bahram Chahardouli, Ali Maleki
Background: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder characterized by immature myeloid cell proliferation and bone marrow failure. Various genetic and epigenetic factors have been found to be influential in such patients. Methylation silencing of APAF-1, a putative tumor suppressor gene (TSG), has been found in several human malignancies. In this study, we explored the association of APAF-1 methylation status with AML patients. Materials and Methods: We studied the methylation status of APAF-1 gene in 101 AML patients and 50 healthy subjects as controls...
July 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/28984348/acute-myeloid-leukaemia-with-gene-mutation-a-correlation-with-haematological-and-immunophenotypic-characteristics-and-our-experience-in-a-tertiary-care-cancer-center-in-south-india
#9
Rachna Khera, Faiq Ahmed, Manasi Mundada, Lavanya Nambaru, Sudha S Murthy, Sandhya Devig, Senthil J Rajappa, Krishna Mohan Mallavarapu, A Santa, Pavan Kumar
OBJECTIVE: Molecular genetic analysis of FLT3, NPM1, and CEBPA is already the standard of care in patients with acute myeloid leukaemia (AML) and represents the most frequent genetic alterations and important diagnostic and prognostic indicators. This study was undertaken to determine the frequency of FLT3 and NPM1 gene mutations in our institution and to characterize the association between gene mutations and haematological parameters as well as immunophenotypic features. MATERIAL AND METHOD: Morphological, haematological and immunophenotypic characteristics of NPM1 and FLT3 mutations in 126 patients of de novo AML including adults and children were studied...
October 6, 2017: Türk Patoloji Dergisi
https://www.readbyqxmd.com/read/28980058/full-length-mutation-search-of-the-tp53-gene-in-acute-myeloid-leukemia-has-increased-significance-as-a-prognostic-factor
#10
Kazuki Terada, Hiroki Yamaguchi, Toshimitsu Ueki, Kensuke Usuki, Yutaka Kobayashi, Kenji Tajika, Seiji Gomi, Saiko Kurosawa, Keiki Miyadera, Taichiro Tokura, Ikuko Omori, Atushi Marumo, Yusuke Fujiwara, Shunsuke Yui, Takeshi Ryotokuji, Yoshiki Osaki, Kunihito Arai, Tomoaki Kitano, Fumiko Kosaka, Satoshi Wakita, Hayato Tamai, Takahiro Fukuda, Koiti Inokuchi
TP53 gene abnormality has been reported to be an unfavorable prognostic factor in acute myeloid leukemia (AML). However, almost all studies of TP53 gene abnormality so far have been limited to mutation searches in the DNA binding domain. As there have been few reports examining both mutation and deletion over the full-length of the TP53 gene, the clinical characteristics of TP53 gene abnormality have not yet been clearly established. In this study, TP53 gene mutation was observed in 7.3% of the total 412 de novo AML cases (33 mutations in 30 cases), with mutation outside the DNA binding domain in eight cases (27%)...
October 4, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28978861/acute-leukemia-in-adolescents-and-young-adults
#11
Daisuke Tomizawa
Both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are common malignant diseases in adolescents and young adults (AYAs). Recent advances in genomic studies have helped us understand the biological nature of acute leukemia in AYAs; higher frequency of Ph-like ALL and rearrangements in DUX4, ERG, MEF2D, and ZNF384 genes in AYAs with ALL and higher frequency of FLT3-ITD, NPM1, IDH1/2, DNMT3A, ASXL1, TET2, and CEBPA mutations in AYAs with AML than that in children. The pediatric-inspired regimen has become a standard treatment approach for AYAs with ALL, but optimal treatment strategy for AYAs with AML is not yet established to date...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28978858/hematopoietic-stem-cell-transplantation-in-the-era-of-molecular-targeted-therapy
#12
Shin Mineishi
Recent developments in the field of molecular targeted therapy are certainly remarkable. However, the role of hematopoietic stem cell transplantation (HSCT) cannot be the same in this trend of targeted therapy. In the past, HSCT was the sole and ultimate treatment for refractory hematological malignancies, mainly because the conditioning regimens were strong and administering any additional therapy was impossible. In recent years, the conditioning regimens have become less intensive, thus enabling the use of additional therapies post-transplantation...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28978829/frontline-treatment-of-aml-in-adults
#13
Toshihiro Miyamoto, Yoshikane Kikushige, And Goichi Yoshimoto
Despite recent progress in diagnosis and leukemogenesis based on genomic landscapes in acute myelogenous leukemia (AML), advances in AML treatment lag behind. Over the past four decades, combination chemotherapy with anthracycline and cytarabine remains the standard induction therapy. Subsequent post-remission consolidation therapy stratifies patients into favorable-risk, intermediate-risk, and unfavorable-risk groups to assign post-remission therapies based on cytogenetic abnormalities and molecular mutations...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28978821/sequential-acquisition-of-mutations-in-myelodysplastic-syndromes
#14
Hideki Makishima
Recent progress in next-generation sequencing technologies allows us to discover frequent mutations throughout the coding regions of myelodysplastic syndromes (MDS), potentially providing us with virtually a complete spectrum of driver mutations in this disease. As shown by many study groups these days, such driver mutations are acquired in a gene-specific fashion. For instance, DDX41 mutations are observed in germline cells long before MDS presentation. In blood samples from healthy elderly individuals, somatic DNMT3A and TET2 mutations are detected as age-related clonal hematopoiesis and are believed to be a risk factor for hematological neoplasms...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28978059/acute-myeloid-leukemia-cells-require-6-phosphogluconate-dehydrogenase-for-cell-growth-and-nadph-dependent-metabolic-reprogramming
#15
Haymanti Bhanot, Ellen L Weisberg, Mamatha M Reddy, Atsushi Nonami, Donna Neuberg, Richard M Stone, Klaus Podar, Ravi Salgia, James D Griffin, Martin Sattler
Acute myeloid leukemia (AML) cells are highly dependent on glycolytic pathways to generate metabolic energy and support cell growth, hinting at specific, targetable vulnerabilities as potential novel targets for drug development. Elevated levels of NADPH, a central metabolic factor involved in redox reactions, are common in myeloid leukemia cells, but the significance or biochemical basis underlying this increase is unknown. Using a small molecule analog that efficiently inhibits NADPH-producing enzymes, we found that AML cells require NADPH homeostasis for cell growth...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28976600/midostaurin-a-new-oral-agent-targeting-flt3-mutant-acute-myeloid-leukemia
#16
Lindsay C Stansfield, Daniel A Pollyea
Acute myeloid leukemia (AML), a clonal hematologic malignancy that results in bone marrow failure, is the most common acute leukemia in adults (median age of diagnosis 67 years), and treatment options, especially in the elderly population, are limited. Induction chemotherapy with 7+3, the combination of continuous-infusion cytarabine and intermittent dosing of an anthracycline administered over 7 and 3 days, respectively, has remained the standard of care since its introduction in 1973 in the United States...
October 4, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28972800/hidden-flt3-d835y-clone-in-flt3-itd-positive-acute-myeloid-leukemia-that-evolved-into-very-late-relapse-with-t-lymphoblastic-leukemia
#17
Seiichiro Katagiri, Tomohiro Umezu, Kenko Azuma, Michiyo Asano, Daigo Akahane, Hideki Makishima, Kenichi Yoshida, Yosaku Watatani, Kenichi Chiba, Satoru Miyano, Seishi Ogawa, Junko H Ohyashiki, Kazuma Ohyashiki
No abstract text is available yet for this article.
October 3, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28968180/immunomodulatory-properties-of-brucella-melitensis-lipopolysaccharide-determinants-on-mouse-dendritic-cells-in-vitro-and-in-vivo
#18
Yun Zhao, Sean Hanniffy, Vilma Arce-Gorvel, Raquel Conde-Alvarez, SangKon Oh, Ignacio Moriyón, Sylvie Mémet, Jean-Pierre Gorvel
The lipopolysaccharide (LPS) is a major virulence factor of Brucella, a facultative intracellular pathogenic Gram-negative bacterium. Brucella LPS exhibits a low toxicity and its atypical structure was postulated to delay the host immune response, favouring the establishment of chronic disease. Here we carried out an in-depth in vitro and in vivo characterisation of the immunomodulatory effects of Brucella LPS on different dendritic cell (DC) subpopulations. By using LPSs from bacteria that share some of Brucella LPS structural features, we demonstrated that the core component of B...
October 2, 2017: Virulence
https://www.readbyqxmd.com/read/28967922/inhibition-of-usp10-induces-degradation-of-oncogenic-flt3
#19
Ellen L Weisberg, Nathan J Schauer, Jing Yang, Ilaria Lamberto, Laura Doherty, Shruti Bhatt, Atsushi Nonami, Chengcheng Meng, Anthony Letai, Renee Wright, Hong Tiv, Prafulla C Gokhale, Maria Stella Ritorto, Virginia De Cesare, Matthias Trost, Alexandra Christodoulou, Amanda Christie, David M Weinstock, Sophia Adamia, Richard Stone, Dharminder Chauhan, Kenneth C Anderson, Hyuk-Soo Seo, Sirano Dhe-Paganon, Martin Sattler, Nathanael S Gray, James D Griffin, Sara J Buhrlage
Oncogenic forms of the kinase FLT3 are important therapeutic targets in acute myeloid leukemia (AML); however, clinical responses to small-molecule kinase inhibitors are short-lived as a result of the rapid emergence of resistance due to point mutations or compensatory increases in FLT3 expression. We sought to develop a complementary pharmacological approach whereby proteasome-mediated FLT3 degradation could be promoted by inhibitors of the deubiquitinating enzymes (DUBs) responsible for cleaving ubiquitin from FLT3...
October 2, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28964959/genetic-variations-of-bone-marrow-mesenchymal-stromal-cells-derived-from-acute-leukemia-and-myelodysplastic-syndrome-by-targeted-deep-sequencing
#20
Kenko Azuma, Tomohiro Umezu, Satoshi Imanishi, Michiyo Asano, Seiichiro Yoshizawa, Seiichiro Katagiri, Kazuma Ohyashiki, Junko H Ohyashiki
Bone marrow mesenchymal stromal cells (MSCs), which support proliferation and differentiation of hematopoietic stem cells, may play a crucial role in the pathogenesis of myeloid neoplasms. To determine whether MSCs in myeloid neoplasms harbor distinct somatic mutations that may affect their function, we used a targeted gene sequencing panel containing 50 myeloid neoplasm-associated genes with coverage of ≥500. We compared the genetic alterations between MSCs and bone marrow hematopoietic (BM) cells from patients with acute leukemia (n=5) or myelodysplastic syndrome (MDS, n=5)...
September 21, 2017: Leukemia Research
keyword
keyword
16235
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"