Approximately 40% of patients affected by core binding factor (CBF) acute myeloid leukemia (AML) ultimately die from the disease. Few prognostic markers have been identified. In this study we reviewed 192 patients with core binding factor acute myeloid leukemia (AML), treated with curative intent (age, 15-79 years) in 11 Italian institutions. Overall, 10-year overall survival (OS), disease-free survival (DFS), and event-free survival were 63.9%, 54.8%, and 49.9%, respectively; patients with the t(8;21) and inv(16) chromosomal rearrangements exhibited significant differences at diagnosis. Despite similarly high complete remission (CR) rate, patients with inv(16) experienced superior DFS and a high chance of achieving a second CR, often leading to prolonged OS also after relapse. We found that a complex karyotype (ie, ≥4 cytogenetic anomalies) affected survival; the KIT D816 mutation predicted worse prognosis only in patients with the t(8;21) rearrangement, whereas FLT3 mutations had no ...
Stem Cells International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies in all areas of stem cell biology and applications. The journal will consider basic, translational, and clinical research, including animal models and clinical trials.
This study is examining the appropriate dose and side effects of dasatinib, when it is given with the standard of care chemotherapy for children and adolescents
KIT is a receptor tyrosine kinase that is functionally relevant for hematopoiesis, mast cell development and function, gametogenesis and melanogenesis. Normal KIT signaling requires binding to stem cell factor, and PI3K-Akt is one of the putative effector pathways. In humans, germline loss-of-function KIT mutations have been associated with piebaldism - an autosomal dominant condition characterized by depigmented patches of skin and hair. Gain-of-function KIT mutations are usually acquired and have been associated with myeloid malignancies including core binding factor acute myeloid leukemia and systemic mastocytosis (SM), germ cell tumors, gastrointestinal stromal tumors and sinonasal T cell lymphomas. KITD816V is the most prevalent KIT mutation in mast cell disease and occurs in more than 90% of the cases that fulfill the World Health Organization diagnostic criteria for SM. However, its precise pathogenetic contribution is not well understood. In clinical practice, SM is considered either indolent or
core binding factor alpha: core binding factor plays a key role in several development pathways and in human disease; has been sequenced
TY - JOUR. T1 - Selection of reversions and suppressors of a mutation in the CBF binding site of a lymphomagenic retrovirus. AU - Martiney, Marita J.. AU - Rulli, Karen. AU - Beaty, Robert. AU - Levy, Laura S.. AU - Lenz, Jack. PY - 1999/8/23. Y1 - 1999/8/23. N2 - The retrovirus SL3 induces T-cell lymphomas in mice. The transcriptional enhancer in the long terminal repeat (LTR) of SL3 contains two 72-bp repeats. Each repeat contains a binding site for the transcription factor CBF (also called AML1). The CBF binding sites are called core elements. SAA is a mutant that is identical to SL3 except for the presence of a single-base-pair substitution in each of the two core elements. This mutation significantly attenuates viral lymphomagenicity. Most lymphomas that occur in SAA-infected mice contain proviruses with reversions or second-site suppressor mutations within the core element. We examined the selective pressures that might account for the predominance of the reversions and suppressor ...
The purpose of the study is to determine whether Fludarabine in combination with cytarabine is more effective than high-dose cytarabine in post-remission
PRIMARY OBJECTIVES:. I. To assess the safety and tolerability of dasatinib with intensive induction therapy (daunorubicin hydrochloride and cytarabine), consolidation chemotherapy (high-dose cytarabine), and as single agent in maintenance therapy in patients with newly diagnosed core-binding factor acute myeloid leukemia (AML).. SECONDARY OBJECTIVES:. I. To assess clinical outcomes such as event-free survival (EFS), complete response (CR) rate, cumulative incidence of relapse (CIR), cumulative incidence of death (CID), disease-free survival (DFS), and overall survival (OS) of patients treated with these regimens.. II. To describe the frequency and severity of adverse events of patients treated on this study during induction, consolidation, and continuation therapy.. III. To describe the interaction of pretreatment disease and patient characteristics including morphology, cytogenetics, immunophenotype, molecular genetic features, white blood cell (WBC) count and hemogram, and performance status ...
The Runx1-CBFbeta transcription factor is required for the emergence of all definitive hematopoietic cells. It is the earliest specific marker of sites from whi...
Among patients with good prognosis core binding factor AML, there is an overall survival rate of only 44%. To understand the genetic factors contributing to poor outcomes within this subgroup, Dr Chew is analysing bone marrow samples collected from 18 patients before and during treatment.. According to Dr Chew, multiple genetic abnormalities acquired during therapy are probably responsible for good prognosis core binding AML developing resistance to chemotherapy.. "To help us predict who will respond poorly to therapy, were identifying the genetic mutations occurring in patients who relapse," he said. "This information will allow us to tailor patient treatment accordingly. Currently a stem cell transplant is considered the definitive treatment and our findings will help clinicians decide if their patients AML will develop resistance and if a stem cell transplant is recommended.". Dr Chew is testing the usefulness of the genetic variations he identifies through an international ...
Disease, Muscle, Muscle Cells, Smooth Muscle, Smooth Muscle Cells, Cells, Heme, Hydrogen, Alkaline Phosphatase, Kidney, Kidney Disease, Osteocalcin, Upregulation, Vascular Calcification, Calcium, Heme Oxygenase, Vascular Smooth Muscle, Atherosclerosis, Bone, Core Binding Factor
This phase II study of romidepsin in relapsed and refractory AML shows that this HDACI has a differential antileukemic activity in patients with CBF AML [predominantly t(8;21)] and that this was associated with an up-regulation of AML1 target genes. These findings are in keeping with observations in vitro that have established that t(8;21) AML is sensitive to therapy with various HDACIs including romidepsin (7, 16-19, 27). Despite the in vitro evidence suggesting an inherent sensitivity of this cytogenetic subset of AML to this class of agents, this is the first study to actually show antileukemic activity in vivo in a cohort of patients with t(8;21) AML and other translocations involving the AML1 gene.. Romidepsin has been investigated in a phase I trial (28) conducted at this dose and schedule in two groups of patients with chronic lymphocytic leukemia and AML, respectively. In that trial that involved 10 AML patients, there were no patients with CBF AML. There were no objective responses ...
Cells, Lead, Acute Myeloid Leukemia, Bone, Bone Marrow, Core-binding Factor, Cytogenetic, Cytogenetic Abnormalities, Disease, Leukemia, Marrow, Myeloid Leukemia, Patient, Patients, Protein Array, Proteins, Regression, Regression Analysis, Ability, Algorithm
Looking for online definition of core-binding factor, runt domain, alpha subunit 3 in the Medical Dictionary? core-binding factor, runt domain, alpha subunit 3 explanation free. What is core-binding factor, runt domain, alpha subunit 3? Meaning of core-binding factor, runt domain, alpha subunit 3 medical term. What does core-binding factor, runt domain, alpha subunit 3 mean?
As per available reports about 248 journals, 14 Conferences and workshops are presently dedicated exclusively to Acute Respiratory Failure and about 1
To study the effects and importance of fluoride on FBs in the development of extraperiosteal calcification and the ossification of skeletal fluorosis, the presence of the osteogenic phenotype, which is indicated by the expression of core-binding factor a1 (Cbfa1) and osteocalcin (OCN), in an FB cell line (L929) and in osteoblasts (OBs) exposed to fluoride was determined. Fibroblasts and osteoblasts were exposed to different concentrations of fluoride (0, 0.0001, 0.001, 0.1, 1.0, 10.0 and 20.0mg/L F-). By using RT-PCR and ELISA, the mRNA levels of Cbfa1 and OCN were measured at 48h, and the protein levels of Cbfa1 and OCN were measured at 2, 4, 24, 48 and 72h. The data demonstrated the following: (1) The Cbfa1 protein level in fluoride-treated fibroblasts clearly increased at 48h in the groups treated with 0.0001, 0.001, 0.1, 1.0 and 20.0mg/L F-. The Cbfa1 protein level of the group treated with 10mg/L F- at 72h was higher than that of the control group. The level of Cbfa1 mRNA in the fibroblasts ...
TY - JOUR. T1 - HDAC1 is a required cofactor of CBFb-SMMHC and a potential therapeutic target in inversion 16 acute myeloid leukemia. AU - Richter, Lisa E.. AU - Wang, Yiqian. AU - Becker, Michelle E.. AU - Coburn, Rachel A.. AU - Williams, Jacob T.. AU - Amador, Catalina. AU - Hyde, R. Katherine. PY - 2019/6/1. Y1 - 2019/6/1. N2 - Acute myeloid leukemia (AML) is a neoplastic disease characterized by the uncontrolled proliferation and accumulation of immature myeloid cells. A common mutation in AML is the inversion of chromosome 16 [inv (16)], which generates a fusion between the genes for core binding factor beta (CBFB) and smooth muscle myosin heavy chain gene (MYH11), forming the oncogene CBFB-MYH11. The expressed protein, CBFb-SMMHC, forms a heterodimer with the key hematopoietic transcription factor RUNX1. Although CBFb-SMMHC was previously thought to dominantly repress RUNX1, recent work suggests that CBFb-SMMHC functions together with RUNX1 to activate transcription of specific target ...
The novel FMS-like tyrosine kinase 3 (FLT3)-N676K point mutation within the FLT3 kinase domain-1 was recently identified in 6 % of de novo acute myeloid leukemia (AML) patients with inv(16). Because FLT3-N676K was encountered almost exclusively in inv(16) AML, we investigated the transforming potential of FLT3-N676K, the cooperation between FLT3-N676K and core binding factor ß-smooth muscle myosin heavy chain (CBFß-SMMHC) (encoded by the inv(16) chimeric gene CBFB-MYH11) in inducing acute leukemia, and tested the sensitivity of FLT3-N676K-positive leukemic cells to FLT3 inhibitors. Retroviral expression of FLT3-N676K in myeloid 32D cells induced AML in syngeneic C3H/HeJ mice (n = 11/13, median latency 58 days), with a transforming activity similar to FLT3-internal tandem duplication (ITD) (n = 8/8), FLT3-TKD D835Y (n = 8/9), and FLT3-ITD-N676K (n = 9/9) mutations. Three out of 14 (21.4 %) C57BL/6J mice transplanted with FLT3-N676K-transduced primary hematopoietic progenitor cells developed ...
Core binding factor (CBF) is a heterodimeric transcription factor that is essential for a number of developmental process including hemotopoiesis and bone development. CBFs contain a DNA-binding CBFα. subunit and a non-DNA binding CBFß. subunit ...
The pathogenesis of PDAC involves genetic alterations, such as K-ras protooncogene mutations, mutations of the p53, p16, and Smad4 tumour suppressor genes, and other less common mutations.2 In addition, there are numerous epigenetic alterations, including altered expression of several growth factors and their receptors.3 For example, PDACs overexpress all TGFβ isoforms and their receptors, and overexpression of these ligands and receptors is often associated with shortened postoperative survival of patients with pancreatic cancer.14,15. The TGFβ pathway is carefully regulated, with Smad proteins as the key component in the signal transduction pathway. In addition, other regulators, such as transcription factors, which facilitate Smad binding to target promoters, may provide routes for feedback and crosstalk.16 For example, members of the CBFA (core binding factor A) family of transcription factors act both as targets and partners of activated Smads. This family, also termed the "Runx family", ...
According to Dr. Stone, MRD status in CBF-AML might also make a difference in treatment selection. A separate study of patients with CBF-AML found that those with an MRD level of at least 1% at one point following induction therapy experienced relapse 90% of the time, with a median remission duration of 10 months (P , .001).4 "This is one group of patients we could justify transplanting," Dr. Stone observed, "but that doesnt mean its going to make a difference.". MRD test results have also been shown to improve outcome prediction,5 albeit modestly, when included with more typical clinical data (ie, age, gender, performance status, white blood cell count, platelet count, bone marrow blast percentage, cytogenetic risk, and NPM1/FLT3-ITD status). Because predictive outcome was only improved by 3%, however, MRD testing is not worth the effort for that reason alone, according to Dr. Stone.. Testing Limitations. Whether performed with multiparameter flow cytometry or next-generation sequencing, MRD ...
Decreased Llgl1 expression has been previously shown to be associated with increased metastatic potential, malignant phenotype, or inferior survival in a variety of solid tumors (Ohali et al., 2004; Schimanski et al., 2005; Kuphal et al., 2006). Given that Llgl1 restrains self-renewal in HSCs and that leukemia is characterized by aberrant activation of self-renewal, we assessed for a role in human AML. First, we asked whether the gene expression signature revealed by genetic inactivation of Llgl1 (Llgl1−/− signature) in HSCs was associated with any genetic subtypes of primary AML. Indeed, clustering based on the Llgl1−/− signature (Fig. 4 B) grouped AML cases into subgroups significantly associated with cytogenetic abnormalities (Fig. 4, B and C). Especially core-binding factor leukemias (t(8;21) and inv(16)) or t(15;17) clustered into specific subgroups. Moreover, the Llgl1−/− signature was most strongly correlated with group 7 based on hierarchical clustering. This group contained ...
Core binding factors are heterodimeric transcription factors involved in diverse developmental processes. They consist of a DNA binding Runx subunit and a non-DNA binding CBFβ sub-unit. Runx proteins are encoded by three genes: Runx1, Runx2 , and ...
Complete information for CBFB gene (Protein Coding), Core-Binding Factor Beta Subunit, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
A series of studies of f-electron systems based on density functional theory methods have been performed. The focus of the studies has been on magnetic and structural properties, as well as investigating ways to handle strong electron correlation in these systems.. A version of the self-interaction correction (SIC) method has been developed for a full-potential linear muffin-tin orbital method. The method is demonstrated to have the strong capabilities of previous SIC implementations, to study energetics and phase stabilities of d- and f-electron systems with localisation-delocalisation transitions, but with no geometrical constraints from the underlying band structure method. The method is applied to the high-TC superconductor CeOFeAs, in which the f-shell of the Ce atoms is argued to undergo a Mott transition to a delocalised state under pressure.. The non-collinear magnetic structures of two rare earth compounds, TbNi5 and CeRhIn5 have been studied, and in both cases the complex magnetic ...
Saturday, October 17, 1953 ld Blinds The Daily Register-Mail, Galesburg, Til- Saturday, October 17, 1953 , 8 GALVA-Meeting of duck hunters of Lake Calhoun Association was held Thursday night at the clubhouse. Plans were made for those Interested to meet at 8 oclock Sunday morning at the clubhouse to build blinds for the hu. Edition of Galesburg Register-Mail
PHP & Kejuruteraan Perisian Projects for $250 - $750. Prescription Pad Writing Software contrive by CompuRx Infotech Pvt. Ltd. is having the ability to check for drug safety at individual disease level like in case of G6PD(40 drugs contraindicated), POR...
The protein encoded by this gene is the beta subunit of a heterodimeric core-binding transcription factor belonging to the PEBP2/CBF transcription factor family which master-regulates a host of genes specific to hematopoiesis (e.g., RUNX1) and osteogenesis (e.g., RUNX2). The beta subunit is a non-DNA binding regulatory subunit; it allosterically enhances DNA binding by alpha subunit as the complex binds to the core site of various enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers and GM-CSF promoters. Alternative splicing generates two mRNA variants, each encoding a distinct carboxyl terminus. In some cases, a pericentric inversion of chromosome 16 [inv(16)(p13q22)] produces a chimeric transcript consisting of the N terminus of core-binding factor beta in a fusion with the C-terminal portion of the smooth muscle myosin heavy chain 11. This chromosomal rearrangement is associated with acute myeloid leukemia of the M4Eo subtype. Two ...
Autor: Otto, Florian et al.; Genre: Zeitschriftenartikel; Im Druck veröffentlicht: 2002-02-13; Keywords: cleidocranial dysplasia; CCD; transcription factor; core binding factor; runt domain; RUNX2; CBFA1; differentiation; osteoblast; Titel: Mutations in the RUNX2 gene in patients with cleidocranial dysplasia
TY - JOUR. T1 - Runx1 expression marks long-term repopulating hematopoietic stem cells in the midgestation mouse embryo. AU - North, Trista E.. AU - De Bruijn, Marella F T R. AU - Stacy, Terryl. AU - Talebian, Laleh. AU - Lind, Evan. AU - Robin, Catherine. AU - Binder, Michael. AU - Dzierzak, Elaine. AU - Speck, Nancy A.. PY - 2002. Y1 - 2002. N2 - Hematopoietic stem cells (HSCs) are first found in the aorta-gonad-mesonephros region and vitelline and umbilical arteries of the midgestation mouse embryo. Runx1 (AML1), the DNA binding subunit of a core binding factor, is required for the emergence and/or subsequent function of HSCs. We show that all HSCs in the embryo express Runx1. Furthermore, HSCs in Runx1+/- embryos are heterogeneous and include CD45+ cells, endothelial cells, and mesenchymal cells. Comparison with wild-type embryos showed that the distribution of HSCs among these various cell populations is sensitive to Runx1 dosage. These data provide the first morphological description of ...
Only the PBM motif is a classic HLH motif. Three different ChIP-chip-derived motifs are all diverse, but all score highly on ChIP-chip data! Are they motifs of other TFs? Check. 602: GCN4; 1095, TEC1; 1096: resembles 602, but is a closer match to CUP9/TOS8. Also hits GCN4. According to the literature (PMID: 9032238) the core binding site for the Rtg1p-Rtg3p heterodimer is 5-GGTCAC-3; the only motif that resembles this is 1446. Vague resemblance to 602 and 1096. I am going to retain 1446, which represents the literature site; PBM motif 870, which resembles an E-box, and ChIP-chip motif 1445, which scores highest on ChIP-chip data. But give all low confidence ...
Runx1 mediates the development of the granular convoluted tubules in the submandibular glands[1] "The mouse granular convoluted tubules (GCTs), which are only located in the submandibular gland (SMG) are known to develop and maintain their structure in an androgen-dependent manner. We previously demonstrated that the GCTs are involuted by the epithelial deletion of core binding factor β (CBFβ), a transcription factor that physically interacts with any of the Runt-related transcription factor (RUNX) proteins (RUNX1, 2 and 3). This result clearly demonstrates that the Runx /Cbfb signaling pathway is indispensable in the development of the GCTs. However, it is not clear which of the RUNX proteins plays useful role in the development of the GCTs by activating the Runx /Cbfb signaling pathway. Past studies have revealed that the Runx /Cbfb signaling pathway plays important roles in various aspects of development and homeostatic events. Moreover, the Runx genes have different temporospatial ...
View mouse Terf2ip Chr8:112011398-112020528 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression