Browsing by Author "Vu, Ly P."

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    A target discovery pipeline identified ILT3 as a target for immunotherapy of multiple myeloma
    (Elsevier, 2023) Di Meo, Francesco; Iyer, Anjushree; Akama, Keith; Cheng, Rujin; Yu, Christina; Cesarano, Annamaria; Kurihara, Noriyoshi; Tenshin, Hirofumi; Aljoufi, Arafat; Marino, Silvia; Soni, Rajesh K.; Roda, Julie; Sissons, James; Vu, Ly P.; Guzman, Monica; Huang, Kun; Laskowski, Tamara; Broxmeyer, Hal E.; Roodman, David G.; Perna, Fabiana; Medicine, School of Medicine
    Multiple myeloma (MM) is an incurable malignancy of plasma cells. To identify targets for MM immunotherapy, we develop an integrated pipeline based on mass spectrometry analysis of seven MM cell lines and RNA sequencing (RNA-seq) from 900+ patients. Starting from 4,000+ candidates, we identify the most highly expressed cell surface proteins. We annotate candidate protein expression in many healthy tissues and validate the expression of promising targets in 30+ patient samples with relapsed/refractory MM, as well as in primary healthy hematopoietic stem cells and T cells by flow cytometry. Six candidates (ILT3, SEMA4A, CCR1, LRRC8D, FCRL3, IL12RB1) and B cell maturation antigen (BCMA) present the most favorable profile in malignant and healthy cells. We develop a bispecific T cell engager targeting ILT3 that shows potent killing effects in vitro and decreased tumor burden and prolonged mice survival in vivo, suggesting therapeutic relevance. Our study uncovers MM-associated antigens that hold great promise for immune-based therapies of MM.
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    PRMT4 blocks myeloid differentiation by assembling a methyl-RUNX1-dependent repressor complex
    (Elsevier B.V., 2013-12-26) Vu, Ly P.; Perna, Fabiana; Wang, Lan; Voza, Francesca; Figueroa, Maria E.; Tempst, Paul; Erdjument-Bromage, Hediye; Gao, Rui; Chen, Sisi; Paietta, Elisabeth; Deblasio, Tony; Melnick, Ari; Liu, Yan; Zhao, Xinyang; Nimer, Stephen D.; Department of Pediatrics, IU School of Medicine
    Defining the role of epigenetic regulators in hematopoiesis has become critically important, as recurrent mutations or aberrant expression of these genes has been identified in both myeloid and lymphoid hematological malignancies. We found that PRMT4, a type I arginine methyltransferase, whose function in normal and malignant hematopoiesis is unknown, is overexpressed in AML patient samples. Overexpression of PRMT4 blocks the myeloid differentiation of human stem/progenitor cells (HSPCs) while its knockdown is sufficient to induce myeloid differentiation of HSPCs. We demonstrated that PRMT4 represses the expression of miR-223 in HSPCs via the methylation of RUNX1, which triggers the assembly of a multi-protein repressor complex that includes DPF2. As part of a feedback loop, PRMT4 expression is repressed post-transcriptionally by miR-223. Depletion of PRMT4 results in differentiation of myeloid leukemia cells in vitro and their decrease proliferation in vivo. Thus, targeting PRMT4 holds potential as a novel therapy for acute myelogenous leukemia.