EVI1 Interferes with Myeloid Maturation via Transcriptional Repression of Cebpa, via Binding to Two Far Downstream Regulatory Elements.

One mechanism by which oncoproteins work is through perturbation of cellular maturation; understanding the mechanisms by which this occurs can lead to the development of targeted therapies. EVI1 is a zinc finger oncoprotein involved in the development of acute myeloid leukemia; previous work has shown it to interfere with the maturation of granulocytes from immature precursors. Here we investigate the mechanism by which that occurs, using an immortalized hematopoietic progenitor cell line, EML-C1, as a model system.

Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia.

The ecotropic virus integration site 1 (EVI1) transcription factor is associated with human myeloid malignancy of poor prognosis and is overexpressed in 8-10% of adult AML and strikingly up to 27% of pediatric MLL-rearranged leukemias. For the first time, we report comprehensive genomewide EVI1 binding and whole transcriptome gene deregulation in leukemic cells using a combination of ChIP-Seq and RNA-Seq expression profiling. We found disruption of terminal myeloid differentiation and cell cycle regulation to be prominent in EVI-induced leukemogenesis.

Immunogenicity of an inactivated monovalent 2009 influenza A (H1N1) vaccine in patients who have cancer.

Background: The immune response of patients who have cancer, who may be receiving immunosuppressive therapy, is generally considered to be decreased. This study aimed to evaluate the immune response of cancer patients to the 2009 influenza A (H1N1) vaccine.

Patients And Methods: We conducted a prospective single site study comparing the immune response after H1N1 vaccination of healthy controls (group A), patients who had solid tumors and were taking myelosuppressive chemotherapy (group B), patients who had solid tumors and were taking nonmyelosuppressive or no treatment (group C), and patients who had hematologic malignancies (group D).

Enhanced histone deacetylase enzyme activity in primary myelofibrosis.

We measured histone deacetylase (HDAC) activity in 17 patients with primary myelofibrosis (PMF); 19 with other myeloproliferative neoplasm (MPN) and 16 normal volunteers. Significantly elevated HDAC levels were shown in patients with PMF compared with other MPN patients and normal volunteers (p<0.05).

Sox4 cooperates with Evi1 in AKXD-23 myeloid tumors via transactivation of proviral LTR.

Myeloid leukemias in AKXD23 mice contain proviral insertions at Evi1, resulting in transcriptional activation. Although Evi1 is clearly involved in leukemia, gene transfer studies in mice with Evi1 fail to cause leukemia, arguing that cooperating events are necessary. We reanalyzed AKXD-23 tumors for cooperating proviral insertion and found that each tumor had a proviral insertion in Sox4, which encodes an HMG-box transcription factor.

Roles of mu-calpain in cultured L8 muscle cells: application of a skeletal muscle-specific gene expression system.

The goal of this work was to characterize the roles of mu-calpain in skeletal muscle protein degradation. Three approaches were developed to alter mu-calpain activity in rat myotubes. These included over-expression of antisense mu-calpain (mu-AS), dominant negative mu-calpain (mu-DN) and the antisense 30-kDa calpain subunit (30-AS).

Development of a ponasterone A-inducible gene expression system for application in cultured skeletal muscle cells.

The goal of this study was to develop an inducible gene expression system to assess functions of specific proteins in differentiated cultured skeletal muscle. We utilized and modified the ecdysone inducible system because others have used this system to express exogenous genes in vitro and in transgenic animals. A limitation of the commercially-available ecdysone system is its constitutive expression in all tissues.