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Marieke (MM) von Lindern PhD


Molecular Biology

'Molecular Characterization of translocation (6;9) in Acute Nonlymphocytic Leukemia'
Promotor: Prof. D. Bootsma
Co-promotor: Dr G. Grosveld
June 1992 - Erasmus University Rotterdam
Research interests
Expansion and differentiation of erythroblasts. We developed an in vitro cell system in which erythroid progenitors can be expanded in presence of Epo, SCF and glucocorticoids, while retaining the capacity to undergo complete and synchronous differentiation to mature erythrocytes. In this model system we study how SCF inhibits differentiation and sustains proliferation of erythroblasts. Since we discovered an important role for selective mRNA translation in erythropoiesis, the mechanism of selective mRNA translation, the role of deregulated translation in anemia, and the cellular processes controlled at the level of selective mRNA translation are at the centre of our investigations.
  • Standard techniques in molecular biology and biochemistry
  • Isolation and analysis of polyribosomes to assay translation initiation
  • Ribosome profiling
  • In vitro culture of primary erythroid cells derived from mouse fetal liver, bone marrow or ES-cells, or from human peripheral blood or bone marrow
2012-presentAssociate professor (UHD) at the Dept Hematology, AMC, UvA, Amsterdam
2010-presentHead of the Dept Hematopoiesis, Sanquin Research and Landsteiner Laboratory
2010-presentAssociate professor (UHD) at the Dept Hematology, ErasmusMC, Rotterdam (as guest)
2006-2010Associate professor (UHD) at the Dept Hematology, ErasmusMC, Rotterdam. Full position
1996-2006Senior scientist at the Dept Hematology, ErasmusMC, Rotterdam
1992-1995Postdoc at the Institute of Molecular Pathology , Vienna, Austria. Studying erythropoiesis with dr. Hartmut Beug
1986-1992PhD studies at the Dept Cell Biology and Genetics, Erasmus University Rotterdam
1986Graduated in Biology, University of Leiden

Other academic activities

2010-presentMember of the Leukemia and Lymphoma Research (LLR, London, UK) research committee
Other professional activities

Chair of the Beug Foundation for Metastasis Research.
The Beug Foundation for Metastasis Research supports basic research on the mechanisms that underlie cancer metastasis, and promotes the cooperation between basic and pharmaceutical research to develop novel therapies.

Sanquin publications
Other publications

van Dijk TB, Gillemans N, Pourfarzad F, van Lom K, von Lindern M, Grosveld F, Philipsen S. (2010) Fetal globin expression is regulated by Friend of Prmt1. Blood 2010 Nov 18;116(20):4349-52.

Borg J, Papadopoulos P, Georgitsi M, Gutiérrez L, Grech G, Fanis P, Phylactides M, Verkerk AJ, van der Spek PJ, Scerri CA, Cassar W, Galdies R, van Ijcken W, Ozgür Z, Gillemans N, Hou J, Bugeja M, Grosveld FG, von Lindern M, Felice AE, Patrinos GP, Philipsen S. Haploinsufficiency for the erythroid transcription factor KLF1 causes hereditary persistence of fetal hemoglobin. Nat Genet 2010 42:801-5.

Rasmussen KD, Simmini S, Abreu-Goodger C, Bartonicek N, Di Giacomo M, Bilbao-Cortes D, Horos R, von Lindern M, Enright AJ, O'Carroll D. The miR-144/451 locus is required for erythroid homeostasis. J Exp Med 2010; 207:1351-8.

Kheradmand Kia S, Solaimani Kartalaei P, Farahbakhshian E, Pourfarzad F, von Lindern M, Verrijzer CP. EZH2-dependent chromatin looping controls INK4a and INK4b, but not ARF, during human progenitor cell differentiation and cellular senescence. Epigenetics Chromatin 2009; 2:16.

Grech G, Blazquez-Domingo M, Kolbus A, Bakker, WJ, Mullner, EW, Beug H, von Lindern M. Igbp1 is part of a positive feedback loop in stem cell factor-dependent, selective mRNA translation initiation inhibiting erythroid differentiation. Blood 2008; 112:2750-60.

Grosso AR, Gomes AQ, Barbosa-Morais NL, Caldeira S, Thorne NP, Grech G, von Lindern M, Carmo-Fonseca M. Tissue-specific splicing factor gene expression signatures. Nucleic Acids Res 2008; 36:4823-32.

Glasow A, Barrett A, Petrie K, Gupta R, Boix-Chornet M, Zhou DC, Grimwade D, Gallagher R, von Lindern M, Waxman S, Enver T, Hildebrandt G, Zelent A. DNA methylation-independent loss of RARA gene expression in acute myeloid leukemia. Blood 2008; 111:2374-7.

Bakker WJ, van Dijk TB, Parren-van Amelsvoort M, Kolbus A, Yamamoto K, Steinlein P, Verhaak RG, Mak TW, Beug H, Lowenberg B, and von Lindern M. Differential regulation of Foxo3a target genes in erythropoiesis. Mol Cell Biol 2007; 27:3839-54.

Ferreira R, Wai A, Shimizu R, Gillemans N, Rottier R, von Lindern M, Ohneda K, Grosveld F, Yamamoto M, Philipsen S. Dynamic regulation of Gata factor levels is more important than their identity. Blood 2007; 109:5481-90.

Kooren J., Palstra RJ, Klous P, Splinter E, von Lindern M, Grosveld F, de Laat W. Beta-globin active chromatin Hub formation in differentiating erythroid cells and in p45 NF-E2 knock-out mice. J Biol Chem 2007; 282:16544-52.

van de Ven M, Andressoo JO, Holcomb VB, von Lindern M, Jong WM, Zeeuw CI, Suh Y, Hasty P, Hoeijmakers JH, van der Horst GT, Mitchell JR. Adaptive Stress Response in Segmental Progeria Resembles Long-Lived Dwarfism and Calorie Restriction in Mice. PLoS Genet 2006; 2:e192.

von Lindern M. Cell-cycle control in erythropoiesis. Blood 2006; 108:781-2.

von Lindern M
. Diamond-Blackfan anemia: a model for control of mRNA translation in hematopoiesis? Haematologica 2005; 90:1441a.

Glasow A, Prodromou N, Xu K, von Lindern M, Zelent A. Retinoids and myelomonocytic growth factors cooperatively activate RARA and induce human myeloid leukemia cell differentiation via MAP kinase pathways. Blood 2005; 105:341-9.

Drissen R, von Lindern M, Kolbus A, Driegen S, Steinlein P, Beug H, Grosveld F, Philipsen S. The erythroid phenotype of EKLF-null mice: defects in hemoglobin metabolism and membrane stability. Mol Cell Biol 2005; 25:5205-14.

Blazquez-Domingo M, Grech G, von Lindern M. Translation initiation factor 4E inhibits differentiation of erythroid progenitors. Mol Cell Biol 2005; 25:8496-506.

von Lindern M
, Schmidt U, Beug H. Control of Erythropoiesis by Erythropoietin and Stem Cell Factor: A Novel Role for Bruton's Tyrosine Kinase. Cell Cycle 2004; 3:876-9.

Van den Akker E, van Dijk T, Parren-van Amelsvoort M, Grossmann K, Schaeper U, Toney-Earley K, Waltz S, Löwenberg B, von Lindern M. The tyrosine kinase receptor RON functions downstream the erythropoietin receptor to induce expansion of erythrothroid progenitors. Blood 2004; 103:4457-65.

Van den Akker E, van Dijk T, Schmidt U, Felida L, Beug H, Löwenberg B, von Lindern M. The BTK Inhibitor LFM-A13 is a Potent Inhibitor of JAK2 Kinase Activity. Biol Chem 2004; 385:409-13.

Schmidt U, van den Akker E, Parren-van Amelsvoort M, Litos G, de Bruijn M, Gutiérrez L, Hendriks R, Ellmeier W, Löwenberg B, Beug H, von Lindern M. Btk is required for an efficient response to erythropoietin and for SCF-controlled protection against TRAIL in erythroid progenitors. J. Exp. Med 2004; 199:785-95.

Joosten M, Blazquez-Domingo M, Lindeboom F, Boulme F, Van Hoven-Beijen A, Habermann B, Lowenberg B, Beug H, Mullner EW, Delwel R, Von Lindern M. Putative protooncogene Nm23-M2: translational control by cytokines via phosphoinositide-3-kinase signaling. J Biol Chem 2004; 38169-76.

Bakker W, Blazquez-Domingo MK, A, Besooyen J, Steinlein P, Beug H, Coffer P, Löwenberg B, von Lindern M, van Dijk T. FoxO3a regulates erythroid differentiation and induces BTG1, an activator of Protein Arginine Methyl Transferase 1. J Cell Biol 2004; 164:175-84.

Looijenga LH, de Leeuw H, van Oorschot M, van Gurp RJ, Stoop H, Gillis AJ, de Gouveia Brazao CA, Weber RF, Kirkels WJ, van Dijk T, von Lindern M, Valk P, Lajos G, Olah E, Nesland JM, Fossa SD, Oosterhuis JW. Stem cell factor receptor (c-KIT) codon 816 mutations predict development of bilateral testicular germ-cell tumors. Cancer Res 2003; 63:7674-8.

Kolbus A, Blazquez-Domingo M, Carotta S, Bakker W, Luedemann S, von Lindern M, Steinlein P, Beug H. Cooperative signaling between cytokine receptors and the glucocorticoid receptor in the expansion of erythroid progenitors: molecular analysis by expression profiling. Blood 2003; 102:3136-46.

Schulte CE, von Lindern M, Steinlein P, Beug H, Wiedemann LM. MLL-ENL cooperates with SCF to transform primary avian multipotent cells. Embo J 2002; 21:4297-306.

de Krom M, van de Corput M, von Lindern M, Grosveld F, Strouboulis J. (2002) Stochastic patterns in globin gene expression are established prior to transcriptional activation and are clonally inherited. Mol Cell 2002; 9:1319-26.

von Lindern M
, Deiner EM, Dolznig H, Parren-Van Amelsvoort M, Hayman MJ, Mullner EW, Beug H. Leukemic transformation of normal murine erythroid progenitors: v- and c-ErbB act through signaling pathways activated by the EpoR and c-Kit in stress erythropoiesis. Oncogene 2001; 20:3651-64.

von Lindern M
, Parren-van Amelsvoort M, van Dijk T, Deiner E, van den Akker E, van Emst-de Vries S, Willems P, Beug H, Lowenberg B. Protein kinase C alpha controls erythropoietin receptor signaling. J Biol Chem 2000; 275:34719-27.

van Dijk TB, van Den Akker E, Amelsvoort MP, Mano H, Lowenberg B, von Lindern M. Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells. Blood 2000; 96:3406-13.

Valk P, Verbakel S, von Lindern M, Lowenberg B, Delwel R. Enhancement of erythropoietin-stimulated cell proliferation by Anandamide correlates with increased activation of the mitogen-activated protein kinases ERK1 and ERK2. Hematol J 2000; 1:254-63.

Wessely O, Bauer A, Quang CT, Deiner EM, von Lindern M, Mellitzer G, Steinlein P, Ghysdael J, Beug H. A novel way to induce erythroid progenitor self renewal: cooperation of c-Kit with the erythropoietin receptor. Biol Chem 1999; 380:187-202.

Von Lindern M, Zauner W, Mellitzer G, Steinlein P, Fritsch G, Huber K, Lowenberg B, Beug H. The glucocorticoid receptor cooperates with the erythropoietin receptor and c-Kit to enhance and sustain proliferation of erythroid progenitors in vitro. Blood 1999; 94:550-9.

Jansen MW, von Lindern M, Beug H, Brandenburg H, Wildschut HI, Wladimiroff JW, In 't Veld PA. (1999) The use of in vitro expanded erythroid cells in a model system for the isolation of fetal cells from maternal blood. Prenat Diagn 1999; 19:323-9.

Von Lindern M, Boer L, Wessely O, Parker M, Beug H. The transactivation domain AF-2 but not the DNA-binding domain of the estrogen receptor is required to inhibit differentiation of avian erythroid progenitors. Mol Endocrinol 1998; 12:263-77.

Tewari R, Gillemans N, Wijgerde M, Nuez B, von Lindern M, Grosveld F, Philipsen S. Erythroid Kruppel-like factor (EKLF) is active in primitive and definitive erythroid cells and is required for the function of 5'HS3 of the beta-globin locus control region. Embo J 1998; 17:2334-41.

Ciana P, Braliou GG, Demay FG, von Lindern M, Barettino D, Beug H, Stunnenberg HG. Leukemic transformation by the v-ErbA oncoprotein entails constitutive binding to and repression of an erythroid enhancer in vivo. Embo J 1998; 17:7382-94.

Wessely O, Deiner EM, Beug H, von Lindern M. The glucocorticoid receptor is a key regulator of the decision between self-renewal and differentiation in erythroid progenitors. Embo J 1997; 16:267-80.

Wessely O, Mellitzer G, von Lindern M, Levitzki A, Gazit A, Ischenko I, Hayman MJ, Beug H. Distinct roles of the receptor tyrosine kinases c-ErbB and c-Kit in regulating the balance between erythroid cell proliferation and differentiation. Cell Growth Differ 1997; 8:481-93.

van't Hof RJ, von Lindern M, Nijweide PJ, Beug H. Stem cell factor stimulates chicken osteoclast activity in vitro. Faseb J 1997; 11:287-93.

Bauer A, Ulrich E, Andersson M, Beug H, von Lindern M. Mechanism of transformation by v-ErbA: substitution for steroid hormone receptor function in self renewal induction. Oncogene 1997; 15:701-15.

Huber K, Wolf H, von Lindern M, Worofka B, Rosen A, Hafner E, Beug H, Philipp K, Bauer K. Development of a rapid means of estimating the haemoglobin F content of candidate fetal cells isolated from maternal blood using HPLC. Prenat Diagn 1996; 16:1011-9.

Beug H, Bauer A, Dolznig H, von Lindern M, Lobmayer L, Mellitzer G, Steinlein P, Wessely O, Mullner E. Avian erythropoiesis and erythroleukemia: towards understanding the role of the biomolecules involved. Biochim Biophys Acta 1996; 1288:M35-47.

Quang CT, Pironin M, von Lindern M, Beug H, Ghysdael J. Spi-1 and mutant p53 regulate different aspects of the proliferation and differentiation control of primary erythroid progenitors. Oncogene 1995; 11:1229-39.

Fornerod M, Boer J, van Baal S, Jaegle M, von Lindern M, Murti KG, Davis D, Bonten J, Buijs A, Grosveld G. Relocation of the carboxyterminal part of CAN from the nuclear envelope to the nucleus as a result of leukemia-specific chromosome rearrangements. Oncogene 1995; 10:1739-48.

Von Lindern M, Fornerod M, van Baal S, Jaegle M, de Wit T, Buijs A, Grosveld G. The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek-can mRNA. Mol Cell Biol 1992; 12:1687-97.

Von Lindern M, van Baal S, Wiegant J, Raap A, Hagemeijer A, Grosveld G. Can, a putative oncogene associated with myeloid leukemogenesis, may be activated by fusion of its 3' half to different genes: characterization of the set gene. Mol Cell Bio 1992; 12:3346-55.

Von Lindern M, Fornerod M, Soekarman N, van Baal S, Jaegle M, Hagemeijer A, Bootsma D, Grosveld G. Translocation t(6;9) in acute non-lymphocytic leukaemia results in the formation of a DEK-CAN fusion gene. Baillieres Clin Haematol 1992; 5:857-79.

Von Lindern M, Breems D, van Baal S, Adriaansen H, Grosveld G. Characterization of the translocation breakpoint sequences of two DEK-CAN fusion genes present in t(6;9) acute myeloid leukemia and a SET-CAN fusion gene found in a case of acute undifferentiated leukemia. Genes Chromosomes Cancer 1992; 5:227-34.

Soekarman D, von Lindern M, Daenen S, de Jong B, Fonatsch C, Heinze B, Bartram C, Hagemeijer A, Grosveld G. The translocation (6;9) (p23;q34) shows consistent rearrangement of two genes and defines a myeloproliferative disorder with specific clinical features. Blood 1992; 79:2990-7.

Soekarman D, von Lindern M, van der Plas DC, Selleri L, Bartram CR, Martiat P, Culligan D, Padua RA, Hasper-Voogt KP, Hagemeijer A, Grosveld G. Dek-can rearrangement in translocation (6;9)(p23;q34). Leukemia 1992; 6:489-94.

Von Lindern M, Poustka A, Lerach H, Grosveld G. The (6;9) chromosome translocation, associated with a specific subtype of acute nonlymphocytic leukemia, leads to aberrant transcription of a target gene on 9q34. Mol Cell Biol 1990; 10:4016-26.

Selleri L, von Lindern M, Hermans A, Meijer D, Torelli G, Grosveld G. Chronic myeloid leukemia may be associated with several bcr-abl transcripts including the acute lymphoid leukemia-type 7 kb transcript. Blood 1990; 75:1146-53.

Von Lindern M, van Agthoven T, Hagemeijer A, Adriaansen H, Grosveld G. The human pim-1 gene is not directly activated by the translocation (6;9) in acute nonlymphocytic leukemia. Oncogene 1989; 4:75-9.

Hermans A, Gow J, Selleri L, von Lindern M, Hagemeijer A, Wiedemann LM, Grosveld G. bcr-abl oncogene activation in Philadelphia chromosome-positive acute lymphoblastic leukemia. Leukemia 1988; 2:628-33.

Meijer D, Hermans A, von Lindern M, van Agthoven T, de Klein A, Mackenbach P, Grootegoed A, Talarico D, Della Valle G, Grosveld G. Molecular characterization of the testis specific c-abl mRNA in mouse. Embo J 1987; 6:4041-8.

Domen J, von Lindern M, Hermans A, Breuer M, Grosveld G, Berns A. Comparison of the human and mouse PIM-1 cDNAs: nucleotide sequence and immunological identification of the in vitro synthesized PIM-1 protein. Oncogene Res 1987; 1:103-12.

Hermans A, Heisterkamp N, von Lindern M, van Baal S, Meijer D, van der Plas D, Wiedemann LM, Groffen J, Bootsma D, Grosveld G. Unique fusion of bcr and c-abl genes in Philadelphia chromosome positive acute lymphoblastic leukemia. Cell 1987; 51:33-40.

Last edited on: 7 May 2014
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