Search results for "leukemia"

Mutational synergy coordinately remodels chromatin accessibility, enhancer landscape and 3-Dimensional DNA topology to alter gene expression during l…

2020

AbstractAltered transcription is a cardinal feature of acute myeloid leukemia (AML), however, exactly how mutations synergize to remodel the epigenetic landscape and rewire 3-Dimensional (3-D) DNA topology is unknown. Here we apply an integrated genomic approach to a murine allelic series that models the two most common mutations in AML, Flt3-ITD and Npm1c. We then deconvolute the contribution of each mutation to alterations of the epigenetic landscape and genome organization, and infer how mutations synergize in the induction of AML. These analyses allow the identification of long-range cis-regulatory circuits, including a novel super-enhancer of the Hoxa locus, as well as larger and more …

Transcriptional regulation of the stem cell leukemia gene by PU.1 and Elf-1.

1998

Abstract The SCL gene, also known astal-1, encodes a basic helix-loop-helix transcription factor that is pivotal for the normal development of all hematopoietic lineages. SCL is expressed in committed erythroid, mast, and megakaryocytic cells as well as in hematopoietic stem cells. Nothing is known about the regulation of SCL transcription in mast cells, and in other lineages GATA-1 is the only tissue-specific transcription factor recognized to regulate the SCL gene. We have therefore analyzed the molecular mechanisms underlyingSCL expression in mast cells. In this paper, we demonstrate that SCL promoter 1a was regulated by GATA-1 together with Sp1 and Sp3 in a manner similar to the situati…

Energy requirement and kinetics of transport of poly(A)-free histone mRNA compared to poly(A)-rich mRNA from isolated L-cell nuclei.

1989

ATP-promoted efflux of poly(A)-rich RNA from isolated nuclei of prelabeled mouse lymphoma L5178y cells has an activation energy of 51.5 kJ/mol, similar to that found for the nuclear envelope nucleoside triphosphatase (48.1 kJ/mol) assumed to be involved in mediating nucleocytoplasmic transport of at least some RNA. Here we show that efflux of two specific poly(A)-rich mRNAs (actin and beta-tubulin) from isolated L-cell nuclei is almost totally dependent on the presence of ATP, while efflux of poly(A)-free histone mRNA (H4, H2B, and H1) also occurs to a marked extent in the absence of this nucleotide. Measurements of temperature dependence of transport rate revealed an activation energy of 5…

Regulation of the tumor marker Fascin by the viral oncoprotein Tax of human T-cell leukemia virus type 1 (HTLV-1) depends on promoter activation and …

2015

AbstractAdult T-cell leukemia/lymphoma is a highly infiltrative neoplasia of CD4+ T-lymphocytes that occurs in about 5% of carriers infected with the deltaretrovirus human T-cell leukemia virus type 1 (HTLV-1). The viral oncoprotein Tax perturbs cellular signaling pathways leading to upregulation of host cell factors, amongst them the actin-bundling protein Fascin, an invasion marker of several types of cancer. However, transcriptional regulation of Fascin by Tax is poorly understood. In this study, we identified a triple mode of transcriptional induction of Fascin by Tax, which requires (1) NF-κB-dependent promoter activation, (2) a Tax-responsive region in the Fascin promoter, and (3) a p…

Post-transplantation cyclophosphamide after HLA identical compared to haploidentical donor transplant in acute myeloid leukemia: a study on behalf of…

2022

Post-transplantation cyclophosphamide (PTCY) effectively prevents graft-versus-host disease (GVHD) after unmanipulated HLA-haploidentical hematopoietic stem cell transplantation (HSCT) and achieves low rates of GVHD in HLA-identical transplantation. To compare the outcomes of haploidentical versus HLA identical HSCT in patients undergoing HSCT for acute myeloid leukemia (AML) using PTCY. We conducted a retrospective study of 229 patients undergoing first HSCT for AML using PTCY with additional immunosuppression, 99 from matched sibling or unrelated donor (MSD/MUD) performed in 3 hospitals and 130 from haploidentical donors (haplo group) performed in 20 hospitals within the Spanish Group of …

29: Rapid expansion of acute myeloid leukemia-reactive cytotoxic T cells from CD8+CD62L+ blood lymphocytes of HLA-matched healthy donors in vitro

2007

CCL3 and CCL4, the Major Chemokines Produced by CD38+ Chronic Lymphocytic Leukemia Cells, Facilitate Microenvironmental Interactions of Neoplastic Ce…

2008

Abstract CD38, a negative prognostic marker for patients with CLL, has been demonstrated to be a key molecule in the interactions occurring in the context of tumor microenvironment, mediating both survival and migratory signals for CLL cells. By taking advantage of gene expression profiling studies (GEP) comparing 11 CD38pos (CD38>30%) and 15 CD38neg (CD38<10%) CLLs, we identified as over-expressed in CD38pos CLL cells: i) genes for the two C-C chemokines CCL3 and CCL4 (median-log difference, MLD-CCL3= 3.5; MLD-CCL4=4.4); real-time quantitative PCR (RTQ-PCR) of selected cases confirmed GEP results; ii) the gene for CD49d (MLD=4.4); a high correlation between CD38 and CD49d pro…

Analysis of the p53 and MDM-2 gene in acute myeloid leukemia

1996

The MDM-2 (murine double minute 2) gene codes for a cellular protein that can bind to the p53 tumor suppressor gene product, thereby functioning as a negative regulator of p53. In order to define the role of the MDM-2 gene in the pathogenesis of human acute myeloid leukemia, the expression and the sequence of the MDM-2 gene were examined in samples of bone marrow and/or peripheral mononuclear cells of 38 patients by using immunostaining, polymerase chain reaction (PCR), single strand conformation polymorphism, and sequencing. Immunohistochemical staining detected a weak accumulation of the MDM-2 protein in AML patients of FAB classification M4 and M5. RT-PCR analysis revealed a heterogeneou…

Antiproliferative activity against leukemia cells of sesquiterpene lactones from the Turkish endemic plant Centaurea drabifolia subsp. detonsa

2017

The apolar organic extract obtained from aerial parts of Centaurea drabifolia Sibth. & Sm. subsp. detonsa (Bornm.) Wagenitz, growing wild in Turkey, was investigated for the first time for its secondary metabolite composition. Seven sesquiterpene lactones belonging to the guaiane class (1-7), including the new compound 4, along with a fatty acid lactone derivative (8), were isolated. The structures of these compounds were established by spectroscopic analysis, including 2D NMR spectroscopic techniques, with the stereostructure of the new guaiane 4 determined with the help of MTPA derivatization. Cytotoxic activities of compounds 1-7 were evaluated against two cancer cell lines, namely acute…

Exploring the anticancer potential of pyrazolo[1,2-a]benzo[1,2,3,4] tetrazin-3-one derivatives: The effect on apoptosis induction, cell cycle and pro…

2013

In order to investigate their anticancer potential, four new pyrazolo[1,2-a]benzo[1,2,3,4]-tetrazinone derivatives, designed through the chemometric protocol VLAK, and three of the most active compounds of the previous series have been evaluated on some cellular events including proliferation, apoptosis induction, and cell cycle. The NCI one dose (10 mu M) screening revealed that the 8,9-di-methyl derivative showed activity against Leukemia (CCRF-CEM) and Colon cancer cell line (COLO 205), reaching 81% and 45% of growth inhibition (GI), respectively. Replacement of the two methyl groups with two chlorine atoms maintained the activity toward Leukemia cell (CCRF-CEM, GI 77%) and selectively e…