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Joost Kluiver
dr.

I have a central role in all research projects focusing on the role of noncoding RNAs. My main aim is to understanding how small and long non-coding RNAs contribute to the pathogenesis of B-cell lymphoma. Ongoing studies include MYC-regulated miRNAs and lncRNAs, as well as miRNA-lncRNA interactions and the role of circular RNAs. We apply state-of-the-art methodology including AGO2-RIP, RNA-FISH and gain- and loss-of-function screens using shRNA and CRISPR-Cas technology.

Core regions in immunoglobulin heavy chain enhancers essential for survival of non-Hodgkin lymphoma cells are identified by a CRISPR interference screen
Published in: Haematologica
Chromosomal translocations in non-Hodgkin lymphoma (NHL) result in activation of oncogenes by placing them under the regulation of immunoglobulin heavy chain (IGH) super-enhancers. Aberrant expression of translocated oncogenes induced by enhancer activity can contribute to lymphomagenesis. The role of the IGH enhancers in normal B-cell development is well established, but knowledge regarding the precise mechanisms of their involvement in control of the translocated oncogenes is limited. The goal of this project was to define the critical regions in the IGH regulatory elements and identify enhancer RNAs (eRNA). We...
Marta Elżbieta Kasprzyk, Weronika Sura, Marta Podralska, Marta Kazimierska, Annika Seitz, Wojciech Łosiewski, Tomasz Woźniak, Jeroen E J Guikema, Arjan Diepstra, Joost Kluiver, Anke Van den Berg, Natalia Rozwadowska, Agnieszka Dzikiewicz-Krawczyk
Circular ZDHHC11 supports Burkitt lymphoma growth independent of its miR-150 binding capacity
Published in: Scientific Reports
We previously showed that MYC promoted Burkitt lymphoma (BL) growth by inhibiting the tumor suppressor miR-150, resulting in release of miR-150 targets MYB and ZDHHC11. The ZDHHC11 gene encodes three different transcripts including a mRNA (pcZDHHC11), a linear long non-coding RNA (lncZDHHC11) and a circular RNA (circZDHHC11). All transcripts contain the same region with 18 miR-150 binding sites. Here we studied the relevance of circZDHHC11, including this miR-150 binding site region, for growth of BL cells. CircZDHHC11 was mainly present in the cytoplasmic fraction in BL cells and...
Yichen Liu, Xing Zhao, Annika Seitz, Annie A Hooijsma, Reyhaneh Ravanbakhsh, Sofia Sheveleva, Debora de Jong, Jasper Koerts, Agnieszka Dzikiewicz-Krawczyk, Anke van den Berg, Lotteke J Y M Ziel-Swier, Joost Kluiver
Detection of circulating tumor DNA in plasma of patients with primary CNS lymphoma by digital droplet PCR
Published in: BMC Cancer
BACKGROUND: Primary central nervous system lymphoma (PCNSL) are rare mature B-cell lymphoproliferative diseases characterized by a high incidence of MYD88 L265P and CD79B Y196 hotspot mutations. Diagnosis of PCNSL can be challenging. The aim of the study was to analyze the detection rate of the MYD88 L265P and CD79B Y196 mutation in cell free DNA (cfDNA) in plasma of patients with PCNSL. METHODS: We analyzed by digital droplet PCR (ddPCR) to determine presence of the MYD88 L265P and CD79B Y196 hotspot mutations in cfDNA isolated from plasma of...
Pinpointing Functionally Relevant miRNAs in Classical Hodgkin Lymphoma Pathogenesis
Published in: Cancers
Classical Hodgkin lymphoma (cHL) is a hematological malignancy of B-cell origin. The tumor cells in cHL are referred to as Hodgkin and Reed-Sternberg (HRS) cells. This review provides an overview of the currently known miRNA-target gene interactions. In addition, we pinpointed other potential regulatory roles of microRNAs (miRNAs) by focusing on genes related to processes relevant for cHL pathogenesis, i.e., loss of B-cell phenotypes, immune evasion, and growth support. A cHL-specific miRNA signature was generated based on the available profiling studies. The interactions relevant for cHL were extracted...
Inhibition of the glutamate-cysteine ligase catalytic subunit with buthionine sulfoximine enhances the cytotoxic effect of doxorubicin and cyclophosphamide in Burkitt lymphoma cells
Published in: Journal of Applied Genetics
Burkitt lymphoma (BL) is a highly aggressive lymphoma that mainly affects children and young adults. Chemotherapy is effective in young BL patients but the outcome in adults is less satisfactory. Therefore, there is a need to enhance the cytotoxic effect of drugs used in BL treatment. Glutathione (GSH) is an important antioxidant involved in processes such as regulation of oxidative stress and drug detoxification. Elevated GSH levels have been observed in many cancers and were associated with chemoresistance. We previously identified GCLC, encoding an enzyme involved in GSH...
Marta Kazimierska, Aleksandra Leśniewska, Anja Bakker, Arjan Diepstra, Marta Elżbieta Kasprzyk, Marta Podralska, Karolina Rassek, Joost Kluiver, Anke van den Berg, Natalia Rozwadowska, Agnieszka Dzikiewicz-Krawczyk