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B Cell Leukemia
The Experts below are selected from a list of 273 Experts worldwide ranked by ideXlab platform
Monica J. Justice – 1st expert on this subject based on the ideXlab platform
Evi3, a zinc-finger protein related to EBFAZ, regulates EBF activity in B–Cell LeukemiaOncogene, 2005Co-Authors: Kathryn E Hentges, Keith C Weiser, Tony Schountz, Lanette S Woodward, Herbert C Morse, Monica J. JusticeAbstract:
Retroviral insertions that activate proto-oncogenes are a primary cause of tumors in certain strains of mice. The AKXD recomBinant inBred mice are predisposed to a variety of Leukemias and lymphomas as a result of viral integration. One common insertion site, the ecotropic viral insertion site 3 ( Evi3 ), has Been implicated in most B–Cell tumors in the AKXD-27 strain. The Evi3 gene encodes a zinc-finger protein with sequence similarity to the Early B–Cell Factor-Associated Zinc-finger gene ( EBFAZ ). We show that the Evi3 gene is overexpressed in several tumors with viral insertions at Evi3 , which results in the upregulation of Early B–Cell Factor ( EBF )-target gene expression, suggesting that Evi3 modulates EBF activity. Reconstitution of primary Leukemia Cells showed that these tumors express high densities of the B–Cell surface proteins CD19 and CD38, which are EBF targets. Using a transactivation assay, we show that the terminal six zinc-fingers of Evi3 are required for modification of EBF activity. This is the first evidence that Evi3 expression in tumors alters the level of EBF target genes, and the first characterization of the Evi3 protein domains required for modulation of EBF activity. Further, these data imply that Evi3 misexpression initiates tumorigenesis By perturBing B–Cell development via an interaction with EBF.
Activation of Hex and mEg5 By retroviral insertion may contriBute to mouse B–Cell LeukemiaOncogene, 1999Co-Authors: G M Hansen, Monica J. JusticeAbstract:
AKXD recomBinant inBred mice develop a variety of Leukemias and lymphomas due to retrovirally mediated insertional activation of Cellular proto-oncogenes. We descriBe a new retroviral insertion site that is the most frequent genetic alteration in AKXD B–Cell Leukemias. Multiple genes flank the site of viral insertion, But the expression of just two, Hex and mEg5, is significantly upregulated. Hex is a divergent homeoBox gene that is transiently expressed in many hematopoietic lineages, suggesting an involvement in Cellular differentiation. mEg5 is a memBer of the Bim-C suBfamily of kinesin related proteins that are necessary for spindle formation and staBilization during mitosis. Our data provide the first genetic evidence for the activation of these genes in Leukemia, and suggest that unscheduled expression of Hex and mEg5 contriButes to the development of B–Cell Leukemia. In addition, this work highlights the use of genomic approaches for the study of position effect mutations.
N R Lemoine – 2nd expert on this subject based on the ideXlab platform
Prime-Boost vaccines encoding an intraCellular idiotype/GM-CSF fusion protein induce protective Cell-mediated immunity in murine pre-B Cell Leukemia.Gene Therapy, 2002Co-Authors: Silvia Pasquini, S Peralta, Edoardo Missiaglia, Luca Carta, N R LemoineAbstract:
Prime-Boost vaccines encoding an intraCellular idiotype/GM-CSF fusion protein induce protective Cell-mediated immunity in murine pre-B Cell Leukemia
Prime-Boost vaccines encoding an intraCellular idiotype/GM-CSF fusion protein induce protective Cell-mediated immunity in murine pre-B Cell LeukemiaGene Therapy, 2002Co-Authors: Silvia Pasquini, S Peralta, Edoardo Missiaglia, Luca Carta, N R LemoineAbstract:
Two vaccines against an intraCellularly expressed B Cell idiotype were assessed for their aBility to induce protective immunity in mice against challenge with a pre-B Cell Leukemia. One vaccine was Based on a plasmid expression vector and the other was a recomBinant vaccinia virus; Both vaccines expressed a polypeptide derived from the complementarity-determining regions (CDR_2-CDR_3) of the leukemic clone-specific immunogloBulin heavy chain (IgH), as a fusion product with mouse granulocyte–macrophage colony-stimulating factor (mGM-CSF). Mice inoculated with either vaccine showed significantly higher survival rates than controls after challenge with Leukemia Cells. However, protection from tumor challenge was optimal when the DNA vaccine was used for priming, followed By a Booster immunization with the vaccinia virus recomBinant. This vaccination protocol induced resistance not only to the first tumor challenge given shortly afterwards, But also to a second challenge given months later. Both CD4^+ and CD8^+ T Cells contriButed to protection in vaccinated mice. These data suggest that such a vaccine regimen might reduce the incidence of recurrence in patients with minimal residual disease after conventional therapy.
Brice J Weinberg – 3rd expert on this subject based on the ideXlab platform
suppression of glut1 and glucose metaBolism By decreased akt mtorc1 signaling drives t Cell impairment in B Cell LeukemiaJournal of Immunology, 2016Co-Authors: Peter J Siska, Brice J Weinberg, Gerritje J W Van Der Windt, Rigel J Kishton, Sivan Cohen, William Eisner, Nancie J Maciver, Arnon P KaterAbstract:
Leukemia can promote T Cell dysfunction and exhaustion that contriButes to increased susceptiBility to infection and mortality. The treatment-independent mechanisms that mediate Leukemia-associated T Cell impairments are poorly understood, But metaBolism tightly regulates T Cell function and may contriBute. In this study, we show that B Cell Leukemia causes T Cells to Become activated and hyporesponsive with increased PD-1 and TIM3 expression similar to exhausted T Cells and that T Cells from leukemic hosts Become metaBolically impaired. MetaBolic defects included reduced Akt/mammalian target of rapamycin complex 1 (mTORC1) signaling, decreased expression of the glucose transporter Glut1 and hexokinase 2, and reduced glucose uptake. These metaBolic changes correlated with increased regulatory T Cell frequency and expression of PD-L1 and Gal-9 on Both leukemic and stromal Cells in the leukemic microenvironment. PD-1, however, was not sufficient to drive T Cell impairment, as in vivo and in vitro anti–PD-1 Blockade on its own only modestly improved T Cell function. Importantly, impaired T Cell metaBolism directly contriButed to dysfunction, as a rescue of T Cell metaBolism By genetically increasing Akt/mTORC1 signaling or expression of Glut1 partially restored T Cell function. Enforced Akt/mTORC1 signaling also decreased expression of inhiBitory receptors TIM3 and PD-1, as well as partially improved antiLeukemia immunity. Similar findings were oBtained in T Cells from patients with acute or chronic B Cell Leukemia, which were also metaBolically exhausted and had defective Akt/mTORC1 signaling, reduced expression of Glut1 and hexokinase 2, and decreased glucose metaBolism. Thus, B Cell Leukemia–induced inhiBition of T Cell Akt/mTORC1 signaling and glucose metaBolism drives T Cell dysfunction.