Selected publications – Metamorphosis-Tx.com

CALUX-STP technology

STAP-STP technology

For conference posters: CONTACT anja.van.de.stolpe@dcdc-tx.com.

Reviews on STAP-STP technology

van de Stolpe, A., Verhaegh, W., Blay, J.-Y., Ma, C.X., Pauwels, P., Pegram, M., Prenen, H., De Ruysscher, D., Saba, N.F., Slovin, S.F., Willard-Gallo, K., Husain, H., 2020. RNA Based Approaches to Profile Oncogenic Pathways From Low Quantity Samples to Drive Precision Oncology Strategies. Front Genet 11, 598118. https://doi.org/10.3389/fgene.2020.598118

van de Stolpe, A., 2019. Quantitative Measurement of Functional Activity of the PI3K Signaling Pathway in Cancer. Cancers (Basel) 11, E293. https://doi.org/10.3390/cancers11030293

Verhaegh, W., van de Stolpe, A., 2014. Knowledge-based computational models. Oncotarget 5, 5196–5197. https://doi.org/10.18632/oncotarget.2276

STAP-STP technology development

Development of Bayesian computational models for Wnt and Estrogen Receptor signal transduction pathways

Verhaegh, W., van Ooijen, H., Inda, M.A., Hatzis, P., Versteeg, R., Smid, M., Martens, J., Foekens, J., van de Wiel, P., Clevers, H., van de Stolpe, A., 2014. Selection of personalized patient therapy through the use of knowledge-based computational models that identify tumor-driving signal transduction pathways. Cancer Res 74, 2936–2945. https://doi.org/10.1158/0008-5472.CAN-13-2515

Development of the PI3K signal transduction pathway model

an Ooijen, H., Hornsveld, M., Dam-de Veen, C., Velter, R., Dou, M., Verhaegh, W., Burgering, B., van de Stolpe, A., 2018. Assessment of Functional Phosphatidylinositol 3-Kinase Pathway Activity in Cancer Tissue Using Forkhead Box-O Target Gene Expression in a Knowledge-Based Computational Model. Am J Pathol 188, 1956–1972. https://doi.org/10.1016/j.ajpath.2018.05.020

Development of the Androgen Receptor, NFkappaB, Hedgehog, and TGFbeta signal transduction pathway models

van de Stolpe, A., Holtzer, L., van Ooijen, H., Inda, M.A. de, Verhaegh, W., 2019. Enabling precision medicine by unravelling disease pathophysiology: quantifying signal transduction pathway activity across cell and tissue types. Sci Rep 9, 1603. https://doi.org/10.1038/s41598-018-38179-x

Development of the Notch signal transduction pathway model

Canté-Barrett, K., Holtzer, L., van Ooijen, H., Hagelaar, R., Cordo’, V., Verhaegh, W., van de Stolpe, A., Meijerink, J.P.P., 2020. A Molecular Test for Quantifying Functional Notch Signaling Pathway Activity in Human Cancer. Cancers (Basel) 12, E3142. https://doi.org/10.3390/cancers12113142

Development of the MAPK signal transduction pathways model

Holtzer, L., Wesseling-Rozendaal, Y., Verhaegh, W., van de Stolpe, A., 2022. Measurement of activity of developmental signal transduction pathways to quantify stem cell pluripotency and phenotypically characterize differentiated cells. Stem Cell Res 61, 102748. https://doi.org/10.1016/j.scr.2022.102748

Development of the JAK-STAT 1/2 and JAK-STAT 3 pathway models

Bouwman, W., Verhaegh, W., Holtzer, L., van de Stolpe, A., 2020. Measurement of Cellular Immune Response to Viral Infection and Vaccination. Front Immunol 11, 575074. https://doi.org/10.3389/fimmu.2020.575074

STAP-STP technology to characterize stem cell differentiation

STAP-STP technology for cancer, clinical

Hendrikse CSE, Theelen PMM, van der Ploeg P, Westgeest HM, Boere IA, Thijs AMJ, Ottevanger PB, van de Stolpe A, Lambrechts S, Bekkers RLM, Piek JMJ. The potential of RAS/RAF/MEK/ERK (MAPK) signaling pathway inhibitors in ovarian cancer: A systematic review and meta-analysis. Gynecol Oncol. 2023 Apr;171:83-94. doi: 10.1016/j.ygyno.2023.01.038. Epub 2023 Feb 24. PMID: 36841040.

Hendrikse CSE, van der Ploeg P, van de Kruis NMA, Wilting JHC, Oosterkamp F, Theelen PMM, Lok CAR, de Hullu JA, Smedts HPM, Vos MC, Pijlman BM, Kooreman LFS, Bulten J, Lentjes-Beer MHFM, Bosch SL, van de Stolpe A, Lambrechts S, Bekkers RLM, Piek JMJ. Functional estrogen receptor signal transduction pathway activity and antihormonal therapy response in low-grade ovarian carcinoma. Cancer. 2023 May 1;129(9):1361-1371. doi: 10.1002/cncr.34661. Epub 2023 Mar 3. PMID: 36867576.

Wesseling-Rozendaal, Y., van Doorn, A., Willard-Gallo, K., van de Stolpe, A., 2022. Characterization of Immunoactive and Immunotolerant CD4+ T Cells in Breast Cancer by Measuring Activity of Signaling Pathways That Determine Immune Cell Function. Cancers (Basel) 14, 490. https://doi.org/10.3390/cancers14030490

Creemers A, van der Zalm AP, van de Stolpe A, Holtzer L, Stoffels M, Hooijer GKJ, Ebbing EA, van Ooijen H, van Brussel AGC, Aussems-Custers EMG, van Berge Henegouwen MI, Hulshof MCCM, Bergman JJGHM, Meijer SL, Bijlsma MF, van Laarhoven HWM. FOXO transcriptional activity is associated with response to chemoradiation in EAC. J Transl Med. 2022 Apr 25;20(1):183. doi: 10.1186/s12967-022-03376-w. PMID: 35468793; PMCID: PMC9036728.

van der Ploeg P, Uittenboogaard A, Bosch SL, van Diest PJ, Wesseling-Rozendaal YJW, van de Stolpe A, Lambrechts S, Bekkers RLM, Piek JMJ. Signal transduction pathway activity in high-grade serous carcinoma, its precursors and Fallopian tube epithelium. Gynecol Oncol. 2022 Apr;165(1):114-120. doi: 10.1016/j.ygyno.2022.01.027. Epub 2022 Feb 2. PMID: 35123772.

van der Ploeg P, Uittenboogaard A, Bucks KMM, Lentjes-Beer MHFM, Bosch SL, van Rumste MME, Vos MC, van Diest PJ, Lambrechts S, van de Stolpe A, Bekkers RLM, Piek JMJ. Cyclic activity of signal transduction pathways in fimbrial epithelium of the human fallopian tube. Acta Obstet Gynecol Scand. 2022 Feb;101(2):256-264. doi: 10.1111/aogs.14306. Epub 2021 Dec 19. PMID: 34927235; PMCID: PMC9564698.

Inda, M.A., van Swinderen, P., van Brussel, A., Moelans, C.B., Verhaegh, W., van Zon, H., den Biezen, E., Bikker, J.W., van Diest, P.J., van de Stolpe, A., 2021. Heterogeneity in Signaling Pathway Activity within Primary and between Primary and Metastatic Breast Cancer. Cancers (Basel) 13, 1345. https://doi.org/10.3390/cancers13061345

van Lieshout L, van der Ploeg P, Wesseling-Rozendaal Y, van de Stolpe A, Bosch S, Lentjes-Beer M, Ottenheijm M, Meriaan A, Vos C, de Hullu J, Massuger L, Bekkers R, Piek J. Survival Is Related to Estrogen Signal Transduction Pathway Activity in Postmenopausal Women Diagnosed with High-Grade Serous Ovarian Carcinoma. Cancers (Basel). 2021 Oct 12;13(20):5101. doi: 10.3390/cancers13205101. PMID: 34680250; PMCID: PMC8533979.

Spaan I, van de Stolpe A, Raymakers RA, Peperzak V. Multiple Myeloma Relapse Is Associated with Increased NFκB Pathway Activity and Upregulation of the Pro-Survival BCL-2 Protein BFL-1. Cancers (Basel). 2021 Sep 17;13(18):4668. doi: 10.3390/cancers13184668. PMID: 34572895; PMCID: PMC8467450.

van der Ploeg P, Uittenboogaard A, Thijs AMJ, Westgeest HM, Boere IA, Lambrechts S, van de Stolpe A, Bekkers RLM, Piek JMJ. The effectiveness of monotherapy with PI3K/AKT/mTOR pathway inhibitors in ovarian cancer: A meta-analysis. Gynecol Oncol. 2021 Nov;163(2):433-444. doi: 10.1016/j.ygyno.2021.07.008. Epub 2021 Jul 10. PMID: 34253390.

van Weelden WJ, Lalisang RI, Bulten J, Lindemann K, van Beekhuizen HJ, Trum H, Boll D, Werner HMJ, van Lonkhuijzen LRCW, Yigit R, Forsse D, Witteveen PO, Galaal K, van Ginkel A, Bignotti E, Weinberger V, Sweegers S, Kroep JR, Cabrera S, Snijders MPLM, Inda MA, Eriksson AGZ; European Network for Individualized Treatment in Endometrial Cancer; Krakstad C, Romano A, van de Stolpe A, Pijnenborg JMA. Impact of hormonal biomarkers on response to hormonal therapy in advanced and recurrent endometrial cancer. Am J Obstet Gynecol. 2021 Oct;225(4):407.e1-407.e16. doi: 10.1016/j.ajog.2021.05.007. Epub 2021 May 19. PMID: 34019887.

van der Ploeg P, van Lieshout LAM, van de Stolpe A, Bosch SL, Lentjes-Beer MHFM, Bekkers RLM, Piek JMJ. Functional estrogen receptor signaling pathway activity in high-grade serous ovarian carcinoma as compared to estrogen receptor protein expression by immunohistochemistry. Cell Oncol (Dordr). 2021 Aug;44(4):951-957. doi: 10.1007/s13402-021-00600-5. Epub 2021 Mar 16. PMID: 33723801; PMCID: PMC8338831.

van Hemert F, Dam-de Veen C, Konings S, van der Ven J, van de Stolpe A. A Novel Dual Antibody Staining Assay to Measure Estrogen Receptor Transcriptional Activity. J Fluoresc. 2021 Jan;31(1):219-227. doi: 10.1007/s10895-020-02635-7. Epub 2020 Nov 17. PMID: 33205346; PMCID: PMC7820081.

van Lieshout L, van de Stolpe A, van der Ploeg P, Bowtell D, de Hullu J, Piek J. Signal Transduction Pathway Activity in High-Grade, Serous Ovarian Carcinoma Reveals a More Favorable Prognosis in Tumors with Low PI3K and High NF-κB Pathway Activity: A Novel Approach to a Long-Standing Enigma. Cancers (Basel). 2020 Sep 18;12(9):2660. doi: 10.3390/cancers12092660. PMID: 32961868; PMCID: PMC7564278.

van Weelden WJ, van der Putten LJM, Inda MA, van Brussel A, Snijders MPLM, Schriever LMM, Bulten J, Massuger LFAG, van de Stolpe A, Pijnenborg JMA. Oestrogen receptor pathway activity is associated with outcome in endometrial cancer. Br J Cancer. 2020 Sep;123(5):785-792. doi: 10.1038/s41416-020-0925-4. Epub 2020 Jun 8. PMID: 32507853; PMCID: PMC7463017.

Sieuwerts AM, Inda MA, Smid M, van Ooijen H, van de Stolpe A, Martens JWM, Verhaegh WFJ. ER and PI3K Pathway Activity in Primary ER Positive Breast Cancer Is Associated with Progression-Free Survival of Metastatic Patients under First-Line Tamoxifen. Cancers (Basel). 2020 Mar 27;12(4):802. doi: 10.3390/cancers12040802. PMID: 32230714; PMCID: PMC7226576.

Inda, M.A., Blok, E.J., Kuppen, P.J.K., Charehbili, A., den Biezen-Timmermans, E.C., van Brussel, A., Fruytier, S.E., Meershoek-Klein Kranenbarg, E., Kloet, S., van der Burg, B., Martens, J.W.M., Sims, A.H., Turnbull, A.K., Dixon, J.M., Verhaegh, W., Kroep, J.R., van de Velde, C.J.H., van de Stolpe, A., 2020. Estrogen Receptor Pathway Activity Score to Predict Clinical Response or Resistance to Neoadjuvant Endocrine Therapy in Primary Breast Cancer. Mol Cancer Ther 19, 680–689. https://doi.org/10.1158/1535-7163.MCT-19-0318

van Boxtel W, Verhaegh GW, van Engen-van Grunsven IA, van Strijp D, Kroeze LI, Ligtenberg MJ, van Zon HB, Hendriksen Y, Keizer D, van de Stolpe A, Schalken JA, van Herpen CM. Prediction of clinical benefit from androgen deprivation therapy in salivary duct carcinoma patients. Int J Cancer. 2020 Jun 1;146(11):3196-3206. doi: 10.1002/ijc.32795. Epub 2019 Dec 12. PMID: 31745978; PMCID: PMC7187215.

P Beachy, S Cai, Y Ma, J Hatakeyama, C Zhao, M Stoffels, W Verhaegh, A van de Stolpe, M Pegram; Abstract P5-03-11: Targeted disruption of transcriptional effector GLI2 attenuates breast tumor growth and metastasis. Cancer Res 15 February 2018; 78 (4_Supplement): P5–03–11. https://doi.org/10.1158/1538-7445.SABCS17-P5-03-11

A. van de Stolpe, W. Verhaegh, L. Holtzer; Philips Research, Eindhoven,
Netherlands. QUANTITATIVE SIGNALING PATHWAY ANALYSIS OF
DIFFUSE INTRINSIC PONTINE GLIOMA IDENTIFIES TWO
SUBTYPES, RESPECTIVELY HIGH TGFΒ/MAPK-AP1 AND HIGH
PI3K/HH PATHWAY ACTIVITY, WHICH ARE POTENTIALLY
CLINICALLY ACTIONABLE. Neuro Oncol. 2019 Sep; 21(Suppl 3): iii11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795031/

STP technology to characterize the immune response

van Wigcheren GF, Cuenca-Escalona J, Stelloo S, Brake J, Peeters E, Horrevorts SK, Frölich S, Ramos-Tomillero I, Wesseling-Rozendaal Y, van Herpen CML, van de Stolpe A, Vermeulen M, de Vries IJM, Figdor CG, Flórez-Grau G. Myeloid-derived suppressor cells and tolerogenic dendritic cells are distinctively induced by PI3K and Wnt signaling pathways. J Biol Chem. 2023 Sep 20:105276. doi: 10.1016/j.jbc.2023.105276.

Bouwman, W., Verhaegh, W., van Doorn, A., van de Stolpe, A., 2021. Measuring host immune response status by simultaneous quantitative measurement of activity of signal transduction pathways that coordinate functional activity of immune cells from innate and adaptive immune system (preprint). Immunology. https://doi.org/10.1101/2021.10.06.463309

STAP-STP technology to characterize the mechanism of disease

Bouwman, W., Verhaegh, W., van de Stolpe, A., 2022. Improved diagnosis of inflammatory bowel disease and prediction and monitoring of response to anti-TNF alpha treatment based on measurement of signal transduction pathway activity. Front. Pharmacol. 13, 1008976. https://doi.org/10.3389/fphar.2022.1008976

Bouwman, W., Verhaegh, W., van de Stolpe, A., 2021. Androgen Receptor Pathway Activity Assay for Sepsis Diagnosis and Prediction of Favorable Prognosis. Front Med (Lausanne) 8, 767145. https://doi.org/10.3389/fmed.2021.767145

Artificial intelligence / machine learning

van Hartskamp, M., Consoli, S., Verhaegh, W., Petkovic, M., van de Stolpe, A., 2019. Artificial Intelligence in Clinical Health Care Applications: Viewpoint. Interact J Med Res 8, e12100. https://doi.org/10.2196/12100

Other relevant publications

Preclinical laboratory disease and toxicology models

Langley, G.R., Adcock, I.M., Busquet, F., Crofton, K.M., Csernok, E., Giese, C., Heinonen, T., Herrmann, K., Hofmann-Apitius, M., Landesmann, B., Marshall, L.J., McIvor, E., Muotri, A.R., Noor, F., Schutte, K., Seidle, T., van de Stolpe, A., Van Esch, H., Willett, C., Woszczek, G., 2017. Towards a 21st-century roadmap for biomedical research and drug discovery: consensus report and recommendations. Drug Discov Today 22, 327–339. https://doi.org/10.1016/j.drudis.2016.10.011

Marx, U., Andersson, T.B., Bahinski, A., Beilmann, M., Beken, S., Cassee, F.R., Cirit, M., Daneshian, M., Fitzpatrick, S., Frey, O., Gaertner, C., Giese, C., Griffith, L., Hartung, T., Heringa, M.B., Hoeng, J., de Jong, W.H., Kojima, H., Kuehnl, J., Leist, M., Luch, A., Maschmeyer, I., Sakharov, D., Sips, A.J.A.M., Steger-Hartmann, T., Tagle, D.A., Tonevitsky, A., Tralau, T., Tsyb, S., van de Stolpe, A., Vandebriel, R., Vulto, P., Wang, J., Wiest, J., Rodenburg, M., Roth, A., 2016. Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing. ALTEX 33, 272–321. https://doi.org/10.14573/altex.1603161

van de Stolpe, A., Kauffmann, R.H., 2015. Innovative human-specific investigational approaches to autoimmune disease. RSC Adv. 5, 18451–18463. https://doi.org/10.1039/C4RA15794J

van de Stolpe, A., den Toonder, J., 2013. Workshop meeting report Organs-on-Chips: human disease models. Lab Chip 13, 3449–3470. https://doi.org/10.1039/c3lc50248a

Groen, R.W.J., Noort, W.A., Raymakers, R.A., Prins, H.-J., Aalders, L., Hofhuis, F.M., Moerer, P., van Velzen, J.F., Bloem, A.C., van Kessel, B., Rozemuller, H., van Binsbergen, E., Buijs, A., Yuan, H., de Bruijn, J.D., de Weers, M., Parren, P.W.H.I., Schuringa, J.J., Lokhorst, H.M., Mutis, T., Martens, A.C.M., 2012. Reconstructing the human hematopoietic niche in immunodeficient mice: opportunities for studying primary multiple myeloma. Blood 120, e9–e16. https://doi.org/10.1182/blood-2012-03-414920

Braam, S.R., Tertoolen, L., van de Stolpe, A., Meyer, T., Passier, R., Mummery, C.L., 2010. Prediction of drug-induced cardiotoxicity using human embryonic stem cell-derived cardiomyocytes. Stem Cell Res 4, 107–116. https://doi.org/10.1016/j.scr.2009.11.004

Langley, G., Austin, C.P., Balapure, A.K., Birnbaum, L.S., Bucher, J.R., Fentem, J., Fitzpatrick, S.C., Fowle, J.R., Kavlock, R.J., Kitano, H., Lidbury, B.A., Muotri, A.R., Peng, S.-Q., Sakharov, D., Seidle, T., Trez, T., Tonevitsky, A., van de Stolpe, A., Whelan, M., Willett, C., 2015. Lessons from Toxicology: Developing a 21st-Century Paradigm for Medical Research. Environ Health Perspect 123, A268-272. https://doi.org/10.1289/ehp.1510345

Stem cell biology

Mummery, C.L., Anja van de Stolpe, Bernard Roelen, Hans Clevers, 2010 / 2014 / 2021. Stem cells: scientific facts and fiction, 1-3rd ed. Academic Press, London; Burlington, MA.

Molecular biology

van de Stolpe, A., Caldenhoven, E., Stade, B.G., Koenderman, L., Raaijmakers, J.A., Johnson, J.P., van der Saag, P.T., 1994. 12-O-tetradecanoylphorbol-13-acetate- and tumor necrosis factor alpha-mediated induction of intercellular adhesion molecule-1 is inhibited by dexamethasone. Functional analysis of the human intercellular adhesion molecular-1 promoter. J Biol Chem 269, 6185–6192.

van der Saag, P.T., Caldenhoven, E., van de Stolpe, A., 1996. Molecular mechanisms of steroid action: a novel type of cross-talk between glucocorticoids and NF-kappa B transcription factors. Eur Respir J Suppl 22, 146s–153s.

van de Stolpe, A., Slycke, A.J., Reinders, M.O., Zomer, A.W.M., Goodenough, S., Behl, C., Seasholtz, A.F., van der Saag, P.T., 2004. Estrogen receptor (ER)-mediated transcriptional regulation of the human corticotropin-releasing hormone-binding protein promoter: differential effects of ERalpha and ERbeta. Mol Endocrinol 18, 2908–2923. https://doi.org/10.1210/me.2003-0446

Immunology

Hobo, W., Strobbe, L., Maas, F., Fredrix, H., Greupink-Draaisma, A., Esendam, B., de Witte, T., Preijers, F., Levenga, H., van Rees, B., Raymakers, R., Schaap, N., Dolstra, H., 2013. Immunogenicity of dendritic cells pulsed with MAGE3, Survivin and B-cell maturation antigen mRNA for vaccination of multiple myeloma patients. Cancer Immunol Immunother 62, 1381–1392. https://doi.org/10.1007/s00262-013-1438-2

van Helden, S.F.G., van den Dries, K., Oud, M.M., Raymakers, R.A.P., Netea, M.G., van Leeuwen, F.N., Figdor, C.G., 2010. TLR4-mediated podosome loss discriminates gram-negative from gram-positive bacteria in their capacity to induce dendritic cell migration and maturation. J Immunol 184, 1280–1291. https://doi.org/10.4049/jimmunol.0900764

Moreau, P., Dimopoulos, M.A., Richardson, P.G., Siegel, D.S., Cavo, M., Corradini, P., Weisel, K., Delforge, M., O’Gorman, P., Song, K., Chen, C., Bahlis, N., Oriol, A., Hansson, M., Kaiser, M., Anttila, P., Raymakers, R., Joao, C., Cook, G., Sternas, L., Biyukov, T., Slaughter, A., Hong, K., Herring, J., Yu, X., Zaki, M., San-Miguel, J., 2017. Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis. Eur J Haematol 99, 199–206. https://doi.org/10.1111/ejh.12903

Netea MG, Hoitink O, Kullberg BJ, van der Meer JW, Raymakers R. Defective interferon-gamma production in patients with hairy cell leukaemia. Neth J Med. 2008 Sep;66(8):340-34. PMID: 1880998

Technical analytical developments

Raaijmakers, M.H.G.P., van Emst, L., de Witte, T., Mensink, E., Raymakers, R.A.P., 2002. Quantitative assessment of gene expression in highly purified hematopoietic cells using real-time reverse transcriptase polymerase chain reaction. Exp Hematol 30, 481–487. https://doi.org/10.1016/s0301-472x(02)00787-7

Hemato-oncology

Franssen, L.E., Nijhof, I.S., Bjorklund, C.C., Chiu, H., Doorn, R., van Velzen, J., Emmelot, M., van Kessel, B., Levin, M.-D., Bos, G.M.J., Broijl, A., Klein, S.K., Koene, H.R., Bloem, A.C., Beeker, A., Faber, L.M., van der Spek, E., Raymakers, R., Sonneveld, P., Zweegman, S., Lokhorst, H.M., Thakurta, A., Qian, X., Mutis, T., van de Donk, N.W.C.J., 2018. Lenalidomide combined with low-dose cyclophosphamide and prednisone modulates Ikaros and Aiolos in lymphocytes, resulting in immunostimulatory effects in lenalidomide-refractory multiple myeloma patients. Oncotarget 9, 34009–34021. https://doi.org/10.18632/oncotarget.26131

Gijzen, K., Raymakers, R.A.P., Broers, K.M., Figdor, C.G., Torensma, R., 2008. Interaction of acute lymphopblastic leukemia cells with C-type lectins DC-SIGN and L-SIGN. Exp Hematol 36, 860–870. https://doi.org/10.1016/j.exphem.2008.02.003

Jansen, B.J.H., Gilissen, C., Roelofs, H., Schaap-Oziemlak, A., Veltman, J.A., Raymakers, R.A.P., Jansen, J.H., Kögler, G., Figdor, C.G., Torensma, R., Adema, G.J., 2010. Functional differences between mesenchymal stem cell populations are reflected by their transcriptome. Stem Cells Dev 19, 481–490. https://doi.org/10.1089/scd.2009.0288

Langemeijer, S.M.C., Kuiper, R.P., Berends, M., Knops, R., Aslanyan, M.G., Massop, M., Stevens-Linders, E., van Hoogen, P., van Kessel, A.G., Raymakers, R.A.P., Kamping, E.J., Verhoef, G.E., Verburgh, E., Hagemeijer, A., Vandenberghe, P., de Witte, T., van der Reijden, B.A., Jansen, J.H., 2009. Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet 41, 838–842. https://doi.org/10.1038/ng.391

Leguit, R.J., Raymakers, R.A.P., Hebeda, K.M., Goldschmeding, R., 2021. CCN2 (Cellular Communication Network factor 2) in the bone marrow microenvironment, normal and malignant hematopoiesis. J Cell Commun Signal 15, 25–56. https://doi.org/10.1007/s12079-020-00602-2

Schaap-Oziemlak, A.M., Raymakers, R.A., Bergevoet, S.M., Gilissen, C., Jansen, B.J.H., Adema, G.J., Kögler, G., le Sage, C., Agami, R., van der Reijden, B.A., Jansen, J.H., 2010. MicroRNA hsa-miR-135b regulates mineralization in osteogenic differentiation of human unrestricted somatic stem cells. Stem Cells Dev 19, 877–885. https://doi.org/10.1089/scd.2009.0112

Spaan, I., Timmerman, L.M., Kimman, T., Slomp, A., Cuenca, M., van Nieuwenhuijzen, N., Moesbergen, L.M., Minnema, M.C., Raymakers, R.A., Peperzak, V., 2021. Direct P70S6K1 inhibition to replace dexamethasone in synergistic combination with MCL-1 inhibition in multiple myeloma. Blood Adv 5, 2593–2607. https://doi.org/10.1182/bloodadvances.2020003624

van den Berk, L.C.J., Jansen, B.J.H., Siebers-Vermeulen, K.G.C., Netea, M.G., Latuhihin, T., Bergevoet, S., Raymakers, R.A., Kögler, G., Figdor, C.C., Adema, G.J., Torensma, R., 2009a. Toll-like receptor triggering in cord blood mesenchymal stem cells. J Cell Mol Med 13, 3415–3426. https://doi.org/10.1111/j.1582-4934.2009.00653.x

van den Berk, L.C.J., Roelofs, H., Huijs, T., Siebers-Vermeulen, K.G.C., Raymakers, R.A., Kögler, G., Figdor, C.G., Torensma, R., 2009b. Cord blood mesenchymal stem cells propel human dendritic cells to an intermediate maturation state and boost interleukin-12 production by mature dendritic cells. Immunology 128, 564–572. https://doi.org/10.1111/j.1365-2567.2009.03142.x

Van Dijk, J.P., Knops, G.H.J.N., Van De Locht, L.T.F., Menke, A.L., Jansen, J.H., Mensink, E.J.B.M., Raymakers, R.A.P., De Witte, T., 2002. Abnormal WT1 expression in the CD34-negative compartment in myelodysplastic bone marrow. Br J Haematol 118, 1027–1033. https://doi.org/10.1046/j.1365-2141.2002.03728.x

van Helden, S.F.G., Krooshoop, D.J.E.B., Broers, K.C.M., Raymakers, R.A.P., Figdor, C.G., van Leeuwen, F.N., 2006. A critical role for prostaglandin E2 in podosome dissolution and induction of high-speed migration during dendritic cell maturation. J Immunol 177, 1567–1574. https://doi.org/10.4049/jimmunol.177.3.1567

van Spriel, A.B., Sofi, M., Gartlan, K.H., van der Schaaf, A., Verschueren, I., Torensma, R., Raymakers, R.A.P., Loveland, B.E., Netea, M.G., Adema, G.J., Wright, M.D., Figdor, C.G., 2009. The tetraspanin protein CD37 regulates IgA responses and anti-fungal immunity. PLoS Pathog 5, e1000338. https://doi.org/10.1371/journal.ppat.1000338

Drug resistance mechanisms in cancer

de Grouw, E.P.L.M., Raaijmakers, M.H.G.P., Boezeman, J.B., van der Reijden, B.A., van de Locht, L.T.F., de Witte, T.J.M., Jansen, J.H., Raymakers, R. a. P., 2006. Preferential expression of a high number of ATP binding cassette transporters in both normal and leukemic CD34+CD38- cells. Leukemia 20, 750–754. https://doi.org/10.1038/sj.leu.2404131

Franssen, L.E., Nijhof, I.S., Couto, S., Levin, M.-D., Bos, G.M.J., Broijl, A., Klein, S.K., Ren, Y., Wang, M., Koene, H.R., Bloem, A.C., Beeker, A., Faber, L.M., van der Spek, E., Raymakers, R., Leguit, R.J., Sonneveld, P., Zweegman, S., Lokhorst, H., Mutis, T., Thakurta, A., Qian, X., van de Donk, N.W.C.J., 2018. Cereblon loss and up-regulation of c-Myc are associated with lenalidomide resistance in multiple myeloma patients. Haematologica 103, e368–e371. https://doi.org/10.3324/haematol.2017.186601

Raaijmakers, H.G.P., Van Den Bosch, G., Boezeman, J., De Witte, T., Raymakers, R. a. P., 2002. Single-cell image analysis to assess ABC-transporter-mediated efflux in highly purified hematopoietic progenitors. Cytometry 49, 135–142. https://doi.org/10.1002/cyto.10157

Raaijmakers, M.H.G.P., de Grouw, E.P.L.M., Heuver, L.H.H., van der Reijden, B.A., Jansen, J.H., Scheffer, G., Scheper, R.J., de Witte, T.J.M., Raymakers, R.A.P., 2005a. Impaired breast cancer resistance protein mediated drug transport in plasma cells in multiple myeloma. Leuk Res 29, 1455–1458. https://doi.org/10.1016/j.leukres.2005.04.013

Raaijmakers, M.H.G.P., de Grouw, E.P.L.M., Heuver, L.H.H., van der Reijden, B.A., Jansen, J.H., Scheper, R.J., Scheffer, G.L., de Witte, T.J.M., Raymakers, R.A.P., 2005b. Breast cancer resistance protein in drug resistance of primitive CD34+38- cells in acute myeloid leukemia. Clin Cancer Res 11, 2436–2444. https://doi.org/10.1158/1078-0432.CCR-04-0212

Raaijmakers, M.H.G.P., de Grouw, E.P.L.M., van der Reijden, B.A., de Witte, T.J.M., Jansen, J.H., Raymakers, R.A.P., 2006. ABCB1 modulation does not circumvent drug extrusion from primitive leukemic progenitor cells and may preferentially target residual normal cells in acute myelogenous leukemia. Clin Cancer Res 12, 3452–3458. https://doi.org/10.1158/1078-0432.CCR-05-1945

Clinical drug repurposing in cancer

Kater, A.P., van Oers, M.H.J., van Norden, Y., van der Straten, L., Driessen, J., Posthuma, W.F.M., Schipperus, M., Chamuleau, M.E.D., Nijland, M., Doorduijn, J.K., Van Gelder, M., Hoogendoorn, M., De Croon, F., Wittebol, S., Kerst, J.M., Marijt, E.W.A., Raymakers, R.A.P., Schaafsma, M.R., Dobber, J.A., Kersting, S., Levin, M.-D., HOVON CLL study group, 2019. Feasibility and efficacy of addition of individualized-dose lenalidomide to chlorambucil and rituximab as first-line treatment in elderly and FCR-unfit patients with advanced chronic lymphocytic leukemia. Haematologica 104, 147–154. https://doi.org/10.3324/haematol.2018.193854

Nijhof, I.S., Franssen, L.E., Levin, M.-D., Bos, G.M.J., Broijl, A., Klein, S.K., Koene, H.R., Bloem, A.C., Beeker, A., Faber, L.M., van der Spek, E., Ypma, P.F., Raymakers, R., van Spronsen, D.-J., Westerweel, P.E., Oostvogels, R., van Velzen, J., van Kessel, B., Mutis, T., Sonneveld, P., Zweegman, S., Lokhorst, H.M., van de Donk, N.W.C.J., 2016. Phase 1/2 study of lenalidomide combined with low-dose cyclophosphamide and prednisone in lenalidomide-refractory multiple myeloma. Blood 128, 2297–2306. https://doi.org/10.1182/blood-2016-07-729236

Oostvogels, R., Jak, M., Raymakers, R., Mous, R., Minnema, M.C., 2018. Efficacy of retreatment with immunomodulatory drugs and proteasome inhibitors following daratumumab monotherapy in relapsed and refractory multiple myeloma patients. Br J Haematol 183, 60–67. https://doi.org/10.1111/bjh.15504

Tjon, J.M.-L., de Groot, M.R., Sypkens Smit, S.M.A., de Wreede, L.C., Snijders, T.J.F., Koene, H.R., Meijer, E., Raaijmakers, M.H.G., Schaap, M., Raymakers, R., Zeerleder, S.S., Halkes, C.J.M., 2018. Short-term efficacy and safety of antithymocyte globulin treatment in elderly patients with acquired aplastic anaemia. Br J Haematol 180, 459–462. https://doi.org/10.1111/bjh.14372

van de Donk, N.W., Görgün, G., Groen, R.W., Jakubikova, J., Mitsiades, C.S., Hideshima, T., Laubach, J., Nijhof, I.S., Raymakers, R.A., Lokhorst, H.M., Richardson, P.G., Anderson, K.C., 2012. Lenalidomide for the treatment of relapsed and refractory multiple myeloma. Cancer Manag Res 4, 253–268. https://doi.org/10.2147/CMAR.S27087

Clinical trial studies in cancer

Peffault de Latour, R., Kulasekararaj, A., Iacobelli, S., Terwel, S.R., Cook, R., Griffin, M., Halkes, C.J.M., Recher, C., Barraco, F., Forcade, E., Vallejo, J.-C., Drexler, B., Mear, J.-B., Smith, A.E., Angelucci, E., Raymakers, R.A.P., de Groot, M.R., Daguindau, E., Nur, E., Barcellini, W., Russell, N.H., Terriou, L., Iori, A.-P., La Rocca, U., Sureda, A., Sánchez-Ortega, I., Xicoy, B., Jarque, I., Cavenagh, J., Sicre de Fontbrune, F., Marotta, S., Munir, T., Tjon, J.M.L., Tavitian, S., Praire, A., Clement, L., Rabian, F., Marano, L., Hill, A., Palmisani, E., Muus, P., Cacace, F., Frieri, C., van Lint, M.-T., Passweg, J.R., Marsh, J.C.W., Socié, G., Mufti, G.J., Dufour, C., Risitano, A.M., Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation, 2022. Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia. N Engl J Med 386, 11–23. https://doi.org/10.1056/NEJMoa2109965

Sonneveld, P., Schmidt-Wolf, I.G.H., van der Holt, B., El Jarari, L., Bertsch, U., Salwender, H., Zweegman, S., Vellenga, E., Broyl, A., Blau, I.W., Weisel, K.C., Wittebol, S., Bos, G.M.J., Stevens-Kroef, M., Scheid, C., Pfreundschuh, M., Hose, D., Jauch, A., van der Velde, H., Raymakers, R., Schaafsma, M.R., Kersten, M.-J., van Marwijk-Kooy, M., Duehrsen, U., Lindemann, W., Wijermans, P.W., Lokhorst, H.M., Goldschmidt, H.M., 2012. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol 30, 2946–2955. https://doi.org/10.1200/JCO.2011.39.6820