foto

Prof. dr. A.P. Kater MD PhD

Main activities
Patient care, Research, Teaching
Focus of research

Research focus on biology and treatment of B-cell malignancies with chronic lymphocytic leukemia (CLL) as main disease serving as a B-cell malignancy model.

Research involves both pre-clinical (cellines, primary CLL cells, mouse models) as well as clinical (phase 1, 2, 3) studies.

The studies are divided in three reserach programs around the central theme: development of, circumvention of and novel strategies for (development of) chemorefractory disease

1. Genetic abberations

2. Intracellular signaling

3. Cross-talk with microenvironment

Key publications
  • Thijssen R, ter Burg J, Garrick B, van Bochove GGW, Brown JR, Fernandes SM, Rodríguez MS, Michot JM, Hallek M, Eichhorst B, Reinhardt HC, Bendell J, Derks IAM, van Kampen RJW, Hege K, Kersten MJ, Trowe T, Filvaroff EH, Eldering E, Kater AP, Dual TORK/DNA-PK inhibition blocks critical signaling pathways in chronic lymphocytic leukemia. BLOOD 2016;128 (4):574-583 [PubMed]
  • Thijssen R, ter Burg J, van Bochove GGW, de Rooij MFM, Kuil A, Jansen MH, Kuijpers TW, Baars JW, Virone-Oddos A, Spaargaren M, Egile C, van Oers MHJ, Eldering E, Kersten MJ , Kater AP, The pan phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor SAR245409 (voxtalisib/XL765) blocks survival, adhesion and proliferation of primary chronic lymphocytic leukemia cells. LEUKEMIA 2016;30 (2):337-345 [PubMed]
  • te Raa GD, Moerland PD, Leeksma AC, Derks IA, Yigittop H, Laddach N, Loden-van Straaten M, Navrkalova V, Trbusek M, Luijks DM, Zenz T, Skowronska A, Hoogendoorn M, Stankovic T, van Oers MH, Eldering E, Kater AP, Assessment of p53 and ATM functionality in chronic lymphocytic leukemia by multiplex ligation-dependent probe amplification. CELL DEATH DIS 2015;6:e1852 [PubMed]
  • te Raa GD, Pascutti MF, García-Vallejo JJ, Reinen E, Remmerswaal EBM, ten Berge IJM, van Lier RAW, Eldering E, van Oers MHJ, Tonino SH, Kater AP, CMV-specific CD8(+) T-cell function is not impaired in chronic lymphocytic leukemia. BLOOD 2014;123 (5):717-724 [PubMed]
  • Lascano V, Guadagnoli M, Schot JG, Luijks DM, Guikema JEJ, Cameron K, Hahne M, Pals S, Slinger E, Kipps TJ, van Oers MHJ, Eldering E, Medema JP, Kater AP, Chronic lymphocytic leukemia disease progression is accelerated by APRIL-TACI interaction in the TCL1 transgenic mouse model. BLOOD 2013;122 (24):3960-3963 [PubMed]
All Publications
Curriculum Vitae

Biographical sketch
Title(s): MD, PhD (dr.)
Name: Arnon (Aron) Philip Kater
Sex: Male
Date and place of birth: 22 October 1972, Amsterdam, the Netherlands Marital state: Married, 2 children

Master’s
University: University of Amsterdam
Date: 01 October 1995
Main Subject: Medicine (cum laude)
Doctorate
University: University of Amsterdam
Date: 02 February 2006
Supervisor/ Promotor: prof. dr. M. H. van Oers
Title of Thesis: Live and let die; Novel apoptosis inducing strategies in chronic lymphocytic leukemia

Professional/work experience
1992 - 1993: Research assistant Lab. Exp. Dermatology, Academic Medical Center (AMC), Amsterdam
1994: Teaching Assistant, Department of Physiology, Faculty of Medicine, University of Amsterdam.
1994: Scientific Research Placement, Department of Biochemistry and Molecular Biology, the George Washington University, Washington DC & Laboratory of Experimental Pulmonology, St. Louis University, St. Louis, Missouri, USA
1998: Voluntary Scientific Research Placement, Dept. of Pediatric Hematology, Emma Children Hospital, Amsterdam
1998 - 1999: Voluntary Scientific Research Placement, Laboratory of Experimental Medicine, AMC
1998 - 2000: Voluntary Scientific Research Placement, Dept of Internal Medicine, Slotervaart hospital in collaboration with St. Elisabeth hospital, Willemstad, Curacao
1999 - 2003: Residency Internal Medicine; AMC and Slotervaart Municipal hospital, Amsterdam;
From 2003: “AGIKO” Medical Doctor in research / clinical research fellow (special version of PhD for MD)
2003 - 2004: PhD student / clinical research fellow, Lab. Of Experimental Immunology, AMC, Amsterdam
2004 - 2005: PhD student / clinical research fellow, Dept. Hematology-Oncology, University of California San Diego, La Jolla, CA, USA
2006: Thesis: Live and let die; Novel apoptosis inducing strategies in chronic lymphocytic leukemia
Oct 2006: Registration as Internist
2006 - 2007: Fellowship Clinical Hematology, Dept. of Internal Medicine, Division of hematology, AMC
Oct 2007: Registration as Hematologist
2007 - present: Member of staff, Department of Internal Medicine, Division of Hematology, AMC
2008 - 2009: Post-doctoral research, Moores Cancer Centre and the Laboratory of Gene Regulation and Signal Transduction, University of California San Diego, CA, USA (as part of NWO-VENI grant)
2010: Group leader of the Hematology group at the laboratory of Experimental Medicine
2012: Appointed as Principal Investigator of the AMC

 


International academic activities

A. MEMBERSHIPS:
• European Research Initiative on CLL (ERIC)
• American Society of Hematology

B. PRESENT INTERNATIONAL ACTIVITIES:
• Research:
o Coordinator European Leukemia Net /ERIC p53-function analysis CLL
o Active research collaboration with international grous; most intense with: dr. T. Zenz (University of Heidelberg, Germany); prof. dr. T. Stankovic (University of Birmingham, UK); dr. M. Lanasa (Duke University Medical Center, Durham NC); prof. dr. T.J. Kipps and prof. dr. M. Karin (University of California San Diego, la Jolla, CA)
• Conferences/committees
o Elected member of the Young Investigator Meeting committee of the International Workshop of CLL (2010, 2011, 2012, 2013)
o Chairman CLL biology session, European Haematology Assocation annual congress (2011)
o Abstract review committee CLL biology section, American Society of Hematology annual congress (2012)
o International Scientific Advisory Board member of the of the Central European Institute of Technology (CEITEC), Brno, Czech Republic on behalf of the European Union (2012 - present)


Other academic activities
A. TEACHING / SUPERVISION:
• (Co-)groupleader/PI of a translational research group consisting of 4 technicians, 5 PhD students and 3 post-docs
• Local, national and international hematology courses (see also E.)
• Local teaching/supervision hematology fellowship program AMC

B. COMMITTEES / STEERING GROUPS:
• Member HOVON CLL working group
• Member steering board HOVON Lunenburg Lymphoma Phase I/II Consortium (LLPC)
• Member of the AMC VENI-support committee

C. CLINICAL TRIALS:
• Principal Investigator both HOVON/LLPC industry sponsored phase 1/2 trials as well as Principal Investigator of an investigator sponsored National HOVON/CLL working group phase 2 trial, National Principal Investigator of a investigator sponsored pan-European German CLL group/HOVON phase 3 trial, and member of global steering board and National Principal Investigator of an industry sponsored global phase 3 trial.


D. REVIEW / EDITORIAL WORK:
• Associated Editor Nederlands Tijdschrift voor Hematologie (Dutch Journal of Haematology)
• Regular reviewer: Blood, British Journal of Haematology, Leukemia, Haematologica, Leukemia & Lymphoma
• Grant reviewer: Dutch Cancer Foundation, UK Lymphoma and Leukemia Research foundation


E. INVITED LECTURES PAST THREE YEARS:
• Multiple lectures at national meetings as well as lectures at the University of Freiburg, the University of Brno, University of Heidelberg, United kingdom National translational CLL meeting, International Workshop of CLL meeting

F. INTERNATIONAL ADVISORY BOARDS PHARMACEUTICAL COMPANIES
• Roche, Johnson & Johnson, Celgene


Non-academic activities
‘07 - present Nederlands Israelitische instelling voor socaiel arbeid
Member of the board

’09 - present Vereniging Centrale Israelitische Ziekenverpleging (CIZ)
President/Chairman of the board; The CIZ is the only remaining jewish hospital in Europe. It was integrated in the early eighties with the Nicolaas Tulp hospital to form the current ziekenhuis Amstelland in Amstelveen. The jewish wing and the jewish identity of the hospital as a whole is the responsibility of the Vereniging CIZ.

Awards
1994 Hippocrates Award
National scientific award for best Dutch student investigator in the field of Medicine
1994 prof. dr. Ph.H. Quanjer Award
Annual student award for best research project supported by the Dutch Asthma Foundation
2004 American Society of Hematology Travel Award
Abstract award for resident physicians
2006 Van Vlissingen Foundation Junior Prize
Award from the van Vlissingen foundation for best thesis in the field of lymphoproliferative diseases in the Netherlands over the last three years; €2000
2007 Jan Swammerdam Award
Award from the Dutch Society of Hematology for most talented hematologist under the age of 45 in the Netherlands; €40.000
2007 van Leeuwen Stipendium
Personal award from the Ruitinga van Swieten foundation for top internists to perform research abroad; €20.000
2011 Dutch Cancer Society Clinical Cancer Research Award
Personal award for clinicians active in oncology/hematology in order to develop their
own research group; €800.000

Grants
1994 Dutch Asthma Foundation student grant and
Dutch Cystic Fibrosis Foundation grant
2002 Dutch Cancer Society research year for residents
Personal grant to perform one year of research during residency; one-year salary and bench-fee
2003 Rene Vogels Foundation travel grant
Personal grant in order to perform research at the University of California San-Diego, USA; €10.000
2004 Dutch Cancer Society Research grant for academics
Personal grant in order to perform research at the University of California San-Diego, USA; living expenses
2007 NWO VENI grant
Personal grant in order to initiate post doctoral studies. This grant was matched by the AMC which enabled me to supervise my first PhD student; NWO €208.000
2009 Dutch Cancer Society project grant; €500.000
2009 Genzyme Europe BV. Research grant; €40.000
2009 Peter vd Laan foundation research grant; €142.750
2009 University of Amsterdam Parelsnoer Research grant; €142.750
2009 Hoffmann-La Roche Ltd research grant; €20.000
2010 Dutch Leukemia foundation research grant; €30.000
2010 Celgene Biopharmaceutical Corporation Clinical and translational research grant; €278.000
2011 Hoffmann-La Roche Ltd research grant; €63.000
2012 Sanofi Aventis Oncology research grant; €80.000
2012 Celgene Biopharmaceutical Corporation basic research grant; €80.000
2012 Dutch Leukemia foundation research grant; €50.000


Publications
International peer-reviewed
1. Kater,A.P., Prins,M.H., von Rosenstiel,I.A., Ottenkamp,J., and Peters,M., Transient thrombocytopenia after cardiac surgery in infants with Down syndrome. J.Pediatr.Hematol.Oncol. 1999. 21: 170-171.
2. Kater,A.P., Heijboer,H., Peters,M., Vogels,T., Prins,M.H., and Heymans,H.S., [Quality of life in children with sickle cell disease in Amsterdam area]. Ned.Tijdschr.Geneeskd. 1999. 143: 2049-2053.
3. Kater,A.P., Westermann,A.M., de Groot,M.R., von dem Borne,A.E., and Kuijper,E.J., Toxin-mediated haemolytic uraemic syndrome without diarrhoea. J.Intern.Med. 2000. 248: 263-265.
4. Schnog,J.B., Kater,A.P., Mac Gillavry,M.R., Duits,A.J., Lard,L.R., van Der Dijs,F.P., Brandjes,D.P., ten,C.H., van Eps,L.W., and Rojer,R.A., Low adjusted-dose acenocoumarol therapy in sickle cell disease: a pilot study. Am.J.Hematol. 2001. 68: 179-183.
5. Kater,A.P., van der Lelie,J., and Levi,M., [Thrombotic microangiopathy: thrombocytopenia and hemolytic anemia]. Ned.Tijdschr.Geneeskd. 2002. 146: 2343-2347.
6. Kater,A.P., Peppelenbosch,M.P., Brandjes,D.P., and Lumbantobing,M., Dichotomal effect of the coumadin derivative warfarin on inflammatory signal transduction. Clin.Diagn.Lab Immunol. 2002. 9: 1396-1397.
7. Kater,A.P. and van Oers,M.H., [Chronic lymphocytic leukemia: high time for a risk-adapted approach]. Ned.Tijdschr.Geneeskd. 2003. 147: 104-109.
8. Kater,A.P., Remmerswaal,E.B., Nolte,M.A., Eldering,E., van Oers,M.H., and van Lier,R.A., Autologous cytomegalovirus-specific T cells as effector cells in immunotherapy of B cell chronic lymphocytic leukaemia. Br.J.Haematol. 2004. 126: 512-516.
9. Kater,A.P., Evers,L.M., Remmerswaal,E.B., Jaspers,A., Oosterwijk,M.F., van Lier,R.A., van Oers,M.H., and Eldering,E., CD40 stimulation of B-cell chronic lymphocytic leukaemia cells enhances the anti-apoptotic profile, but also Bid expression and cells remain susceptible to autologous cytotoxic T-lymphocyte attack. Br.J.Haematol. 2004. 127: 404-415.
10. Dicker,F., Kater,A.P., Fukuda,T., and Kipps,T.J., Fas-ligand (CD178) and TRAIL synergistically induce apoptosis of CD40-activated chronic lymphocytic leukemia B cells. Blood 2005. 105: 3193-3198.
11. Kater,A.P., Dicker,F., Mangiola,M., Welsh,K., Houghten,R., Ostresh,J., Nefzi,A., Reed,J.C., Pinilla,C., and Kipps,T.J., Inhibitors of XIAP sensitize CD40-activated chronic lymphocytic leukemia cells to CD95-mediated apoptosis. Blood 2005. 106: 1742-1748.
12. Mackus,W.J., Kater,A.P., Grummels,A., Evers,L.M., Hooijbrink,B., Kramer,M.H., Castro,J.E., Kipps,T.J., van Lier,R.A., van Oers,M.H., and Eldering,E., Chronic lymphocytic leukemia cells display p53-dependent drug-induced Puma upregulation. Leukemia 2005. 19: 427-434.
13. Dicker,F., Kater,A.P., Prada,C.E., Fukuda,T., Castro,J.E., Sun,G., Wang,J.Y., and Kipps,T.J., CD154 induces p73 to overcome the resistance to apoptosis of chronic lymphocytic leukemia cells lacking functional p53. Blood 2006. 108: 3450-3457.
14. Rubin,B.K., Kater,A.P., and Goldstein,A.L., Thymosin beta4 sequesters actin in cystic fibrosis sputum and decreases sputum cohesivity in vitro. Chest 2006. 130: 1433-1440.
15. Bouw,J., Kater,A.P., van,T.J., and Schultz,M.J., Upper-airway obstruction instigated by Sweet's syndrome. Med.Sci.Monit. 2007. 13: CS53-CS55.
16. Kater,A., Henke,M.O., and Rubin,B.K., The role of DNA and actin polymers on the polymer structure and rheology of cystic fibrosis sputum and depolymerization by gelsolin or thymosin beta 4. Ann.N.Y.Acad.Sci. 2007. 1112: 140-153.
17. Kater,A.P., van Oers,M.H., and Kipps,T.J., Cellular immune therapy for chronic lymphocytic leukemia. Blood 2007. 110: 2811-2818.
18. Smit,L.A., Hallaert,D.Y., Spijker,R., de,G.B., Jaspers,A., Kater,A.P., van Oers,M.H., van Noesel,C.J., and Eldering,E., Differential Noxa/Mcl-1 balance in peripheral versus lymph node chronic lymphocytic leukemia cells correlates with survival capacity. Blood 2007. 109: 1660-1668.
19. Choi,G., van den Borne,M.P., Visser,C.E., Kersten,M.J., and Kater,A.P., Invasive infections with a coagulase-negative staphylococcus in an immunocompromised patient: case report and review of the literature. Ann.Hematol. 2008. 87: 771-772.
20. Hallaert,D.Y., Jaspers,A., van Noesel,C.J., van Oers,M.H., Kater,A.P., and Eldering,E., c-Abl kinase inhibitors overcome CD40-mediated drug resistance in CLL: implications for therapeutic targeting of chemoresistant niches. Blood 2008. 112: 5141-5149.
21. Sonke,G.S., Ludwig,I., van,O.H., Baars,J.W., Meijer,E., Kater,A.P., and de,J.D., Poor outcomes of chronic active Epstein-Barr virus infection and hemophagocytic lymphohistiocytosis in non-Japanese adult patients. Clin.Infect.Dis. 2008. 47: 105-108.
22. Tonino,S.H., Spijker,R., Luijks,D.M., van Oers,M.H., and Kater,A.P., No convincing evidence for a role of CD31-CD38 interactions in the pathogenesis of chronic lymphocytic leukemia. Blood 2008. 112: 840-843.
23. van Dam,I.E., Kater,A.P., Hart,W., and van den Born,B.J., [Severe anaemia caused by Human Parvovirus B19 infection in a patient with autoimmune haemolytic anaemia and a B-cell non-Hodgkin lymphoma]. Ned.Tijdschr.Geneeskd. 2008. 152: 153-157.
24. van,G.R., Kater,A.P., Otto,S.A., Jaspers,A., Borghans,J.A., Vrisekoop,N., Ackermans,M.A., Ruiter,A.F., Wittebol,S., Eldering,E., van Oers,M.H., Tesselaar,K., Kersten,M.J., and Miedema,F., In vivo dynamics of stable chronic lymphocytic leukemia inversely correlate with somatic hypermutation levels and suggest no major leukemic turnover in bone marrow. Cancer Res. 2008. 68: 10137-10144.
25. Enzler,T., Kater,A.P., Zhang,W., Widhopf,G.F., Chuang,H.Y., Lee,J., Avery,E., Croce,C.M., Karin,M., and Kipps,T.J., Chronic lymphocytic leukemia of Emu-TCL1 transgenic mice undergoes rapid cell turnover that can be offset by extrinsic CD257 to accelerate disease progression. Blood 2009. 114: 4469-4476.
26. Mous,R., Jaspers,A., Luijks,D.M., Mellink,C.H., van Oers,M.H., Kater,A.P., and Eldering,E., Detection of p53 dysfunction in chronic lymphocytic leukaemia cells through multiplex quantification of p53 target gene induction. Leukemia 2009. 23: 1352-1355.
27. Zenz,T., Mohr,J., Eldering,E., Kater,A.P., Buhler,A., Kienle,D., Winkler,D., Durig,J., van Oers,M.H., Mertens,D., Dohner,H., and Stilgenbauer,S., miR-34a as part of the resistance network in chronic lymphocytic leukemia. Blood 2009. 113: 3801-3808.
28. Kater,A.P. and Tonino,S.H., Standards for the treatment of relapsed chronic lymphocytic leukemia: a case-based study. Clin.Lymphoma Myeloma.Leuk. 2010. 10 Suppl 1: S34-S41.
29. Tonino,S.H., van,G.M., Eldering,E., van Oers,M.H., and Kater,A.P., R-DHAP is effective in fludarabine-refractory chronic lymphocytic leukemia. Leukemia 2010. 24: 652-654.
30. Tromp,J.M., Tonino,S.H., Elias,J.A., Jaspers,A., Luijks,D.M., Kater,A.P., van Lier,R.A., van Oers,M.H., and Eldering,E., Dichotomy in NF-kappaB signaling and chemoresistance in immunoglobulin variable heavy-chain-mutated versus unmutated CLL cells upon CD40/TLR9 triggering. Oncogene 2010. 29: 5071-5082.
31. Zhang,W., Kater,A.P., Widhopf,G.F., Chuang,H.Y., Enzler,T., James,D.F., Poustovoitov,M., Tseng,P.H., Janz,S., Hoh,C., Herschman,H., Karin,M., and Kipps,T.J., B-cell activating factor and v-Myc myelocytomatosis viral oncogene homolog (c-Myc) influence progression of chronic lymphocytic leukemia. Proc.Natl.Acad.Sci.U.S.A 2010. 107: 18956-18960.
32. Fischer,K., Shanafelt,T., and Kater,A.P., Highlights of the 5th Young Investigators' Meeting on chronic lymphocytic leukemia. Leuk.Lymphoma 2011. 52: 1391-1393.
33. Guadagnoli,M., Kimberley,F.C., Phan,U., Cameron,K., Vink,P.M., Rodermond,H., Eldering,E., Kater,A.P., van,E.H., and Medema,J.P., Development and characterization of APRIL antagonistic monoclonal antibodies for treatment of B-cell lymphomas. Blood 2011. 117: 6856-6865.
34. Kater,A.P., Wittebol,S., Chamuleau,M.E., van,G.M., Oers MH,J.v., and Hovon CLL,W.P., Dutch guidelines for diagnosis and treatment of chronic lymphocytic leukaemia 2011. Neth.J.Med. 2011. 69: 422-429.
35. Mohr,J., Helfrich,H., Fuge,M., Eldering,E., Buhler,A., Winkler,D., Volden,M., Kater,A.P., Mertens,D., Te,R.D., Dohner,H., Stilgenbauer,S., and Zenz,T., DNA damage-induced transcriptional program in CLL: biological and diagnostic implications for functional p53 testing. Blood 2011. 117: 1622-1632.
36. Te Raa,G.D., Fischer,K., Verweij,W., van Houte,A.J., Kater,A.P., and Biesma,D.H., Use of the CD19 count in a primary care laboratory as a screening method for B-cell chronic lymphoproliferative disorders in asymptomatic patients with lymphocytosis. Clin.Chem.Lab Med. 2011. 49: 115-120.
37. Tonino,S.H., van,L.J., van Oers,M.H., Wang,J.Y., Eldering,E., and Kater,A.P., ROS-mediated upregulation of Noxa overcomes chemoresistance in chronic lymphocytic leukemia. Oncogene 2011. 30: 701-713.
38. Tonino,S.H., Rijssenbeek,A.L., Oud,M.E., Pals,S.T., van Oers,M.H., and Kater,A.P., Intracerebral infiltration as the unique cause of the clinical presentation of chronic lymphocytic leukemia/small lymphocytic leukemia. J.Clin.Oncol. 2011. 29: e837-e839.
39. Vos,J.M., Bordbar,A., Vet,R.J., Pals,S.T., and Kater,A.P., Waxing and waning intravascular large cell lymphoma with widespread organ infiltration. Leuk.Lymphoma 2011. 52: 705-708.
40. Lapid,O., van der Horst,C.M., and Kater,A.P., Donor-derived fat tissue as a source for lipofilling after allogeneic hematopoietic cell transplantation. J.Clin.Oncol. 2012. 30: e154-e155.
41. Pospisilova,S., Gonzalez,D., Malcikova,J., Trbusek,M., Rossi,D., Kater,A.P., Cymbalista,F., Eichhorst,B., Hallek,M., Dohner,H., Hillmen,P., van,O.M., Gribben,J., Ghia,P., Montserrat,E., Stilgenbauer,S., and Zenz,T., ERIC recommendations on TP53 mutation analysis in chronic lymphocytic leukemia. Leukemia 2012. 26: 1458-1461.
42. Te Raa,G.D., Tonino,S.H., Remmerswaal,E.B., van Houte,A.J., Koene,H.R., van Oers,M.H., and Kater,A.P., Chronic lymphocytic leukemia specific T-cell subset alterations are clone-size dependent and not present in monoclonal B lymphocytosis. Leuk.Lymphoma 2012. 53: 2321-2325.
43. Te Raa,G.D., van Oers,M.H., and Kater,A.P., Monoclonal B-cell lymphocytosis: recommendations from the Dutch Working Group on CLL for daily practice. Neth.J.Med. 2012. 70: 236-241.
44. Tonino,S.H., van de Berg,P.J., Yong,S.L., Ten Berge,I.J., Kersten,M.J., van Lier,R.A., van Oers,M.H., and Kater,A.P., Expansion of effector T cells associated with decreased PD-1 expression in patients with indolent B cell lymphomas and chronic lymphocytic leukemia. Leuk.Lymphoma 2012. 53: 1785-1794.
45. Tromp,J.M., Geest,C.R., Breij,E.C., Elias,J.A., van,L.J., Luijks,D.M., Kater,A.P., Beaumont,T., van Oers,M.H., and Eldering,E., Tipping the Noxa/Mcl-1 balance overcomes ABT-737 resistance in chronic lymphocytic leukemia. Clin.Cancer Res. 2012. 18: 487-498.
46. van den Broek,E.C., Kater,A.P., van de Schans,S.A., Karim-Kos,H.E., Janssen-Heijnen,M.L., Peters,W.G., Nooijen,P.T., Coebergh,J.W., and Posthuma,E.F., Chronic lymphocytic leukaemia in the Netherlands: trends in incidence, treatment and survival, 1989-2008. Eur.J.Cancer 2012. 48: 889-895.
47. de,W., I, Eldering,E., van Oers,M.H., and Kater,A.P., The biological rationale and clinical efficacy of inhibition of signaling kinases in chronic lymphocytic leukemia. Leuk.Res. 2013. 37: 838-847.
48. Hoogeboom,R., van Kessel,K.P., Hochstenbach,F., Wormhoudt,T.A., Reinten,R.J., Wagner,K., Kater,A.P., Guikema,J.E., Bende,R.J., and van Noesel,C.J., A mutated B cell chronic lymphocytic leukemia subset that recognizes and responds to fungi. J.Exp.Med. 2013. 210: 59-70.
49. Jethwa,A., Hullein,J., Stolz,T., Blume,C., Sellner,L., Jauch,A., Sill,M., Kater,A.P., Te Raa,G.D., Geisler,C., van,O.M., Dietrich,S., Dreger,P., Ho,A.D., Paruzynski,A., Schmidt,M., von,K.C., Glimm,H., and Zenz,T., Targeted resequencing for analysis of clonal composition of recurrent gene mutations in chronic lymphocytic leukaemia. Br.J.Haematol. 2013. 163: 496-500.
50. Kater,A.P., The half-life of guidelines for Waldenstrom's macroglobulinaemia; short stickiness for a sticky disease? Neth.J.Med. 2013. 71: 52-53.
51. Kater,A.P., Spiering,M., Liu,R.D., Doreen Te,R.G., Slinger,E., Tonino,S.H., Beckers,M.M., Daenen,S., Doorduijn,J.K., Lankheet,N.A., Luijks,D.M., Eldering,E., and van Oers,M.H., Dasatinib in combination with fludarabine in patients with refractory chronic lymphocytic leukemia: A multicenter phase 2 study. Leuk.Res. 2013.
52. Lanasa,M.C., Kater,A.P., Shanafelt,T., and Fischer,K., Highlights of the 7th young investigators' meeting on chronic lymphocytic leukemia. Leuk.Lymphoma 2013. 54: 1815-1816.
53. Lascano,V., Guadagnoli,M., Schot,J.G., Luijks,D.M., Guikema,J.E., Cameron,K., Hahne,M., Pals,S., Slinger,E., Kipps,T.J., van Oers,M.H., Eldering,E., Medema,J.P., and Kater,A.P., Chronic lymphocytic leukemia disease progression is accelerated by APRIL-TACI interaction in the TCL1 transgenic mouse model. Blood 2013. 122: 3960-3963.
54. Oostvogels,R., Minnema,M.C., van,E.M., Spaapen,R.M., Te Raa,G.D., Giovannone,B., Buijs,A., van,B.D., Kater,A.P., Griffioen,M., Spierings,E., Lokhorst,H.M., and Mutis,T., Towards effective and safe immunotherapy after allogeneic stem cell transplantation: identification of hematopoietic-specific minor histocompatibility antigen UTA2-1. Leukemia 2013. 27: 642-649.
55. Pascutti,M.F., Jak,M., Tromp,J.M., Derks,I.A., Remmerswaal,E.B., Thijssen,R., van Attekum,M.H., van Bochove,G.G., Luijks,D.M., Pals,S.T., van Lier,R.A., Kater,A.P., van Oers,M.H., and Eldering,E., IL-21 and CD40L signals from autologous T cells can induce antigen-independent proliferation of CLL cells. Blood 2013. 122: 3010-3019.
56. Te Raa,G.D., Malcikova,J., Pospisilova,S., Trbusek,M., Mraz,M., Garff-Tavernier,M.L., Merle-Beral,H., Lin,K., Pettitt,A.R., Merkel,O., Stankovic,T., van Oers,M.H., Eldering,E., Stilgenbauer,S., Zenz,T., and Kater,A.P., Overview of available p53 function tests in relation to TP53 and ATM gene alterations and chemoresistance in chronic lymphocytic leukemia. Leuk.Lymphoma 2013. 54: 1849-1853.
57. Te Raa,G.D., Pascutti,M.F., Garcia-Vallejo,J.J., Reinen,E., Remmerswaal,E.B., Ten Berge,I.J., van Lier,R.A., Eldering,E., van Oers,M.H., Tonino,S.H., and Kater,A.P., CMV-specific CD8+ T cell function is not impaired in chronic lymphocytic leukemia. Blood 2013.

 


National/Dutch peer-reviewed
Kater,A.P., Heijboer,H., Peters,M., Vogels,T., Prins,M.H., and Heymans,H.S., [Quality of life in children with sickle cell disease in Amsterdam area]. Ned.Tijdschr.Geneeskd. 1999. 143: 2049-2053.
Kater,A.P., van der Lelie,J., and Levi,M., [Thrombotic microangiopathy: thrombocytopenia and hemolytic anemia]. Ned.Tijdschr.Geneeskd. 2002. 146: 2343-2347.
Kater,A.P. and van Oers,M.H., [Chronic lymphocytic leukemia: high time for a risk-adapted approach]. Ned.Tijdschr.Geneeskd. 2003. 147: 104-109.
Kater,A.P., Nieuwe apoptose-inducerende strategieën bij chronische lymfatische leukemie. Ned. Tijdschr. Hemat. 2007;4:77-80.
van Dam,I.E., Kater,A.P., Hart,W., and van den Born,B.J., [Severe anaemia caused by Human Parvovirus B19 infection in a patient with autoimmune haemolytic anaemia and a B-cell non-Hodgkin lymphoma]. Ned.Tijdschr.Geneeskd. 2008. 152: 153-157.
Kater, A.P., Van Oers, M.H., De tyrosinekinaseremmer Dasatinib voor behandeling van chemotherapie refractaire chronische lymfatische leukemie: de D’ACCORD-studie. Ned. Tijdschr. Hemat. 2009;6:317-20.
Kater, A.P., Wittebol, S., Chamuleau, M.E., van Gelde,r M., van Oers, M.H. Richtlijnen diagnostiek en behandeling chronische lymfatische leukemie. Ned. Tijdschr. Hemat. 2011;8:190-201.

te Raa, G.D., van Oers, M.H., Kater, A.P. Monoklonale B-cellymfocytose: incidentie, risicostratificatie en aanbevelingen voor de dagelijkse praktijk. Ned. Tijdschr. Hemat.2012;9:138-46.

Kater, A.P., Chamuleau, M.E., Posthuma, W., Schipperus, M.R., Spiering, M., van Oers, M.H. HOVON 109: de effectiviteit en veiligheid van eerstelijnsbehandeling van chronische lymfatische leukemie met chloorambucil, rituximab en lenalidomide bij oudere patiënten en patiënten met comorbiditeit; een fase I/II-studie. Ned. Tijdschr. Hemat. 2012;9:197-201.

de Weerdt, I., Eldering, E.,van Oers, M.H., Kater, A.P. Nieuwe kinase remmers in chronische lymfatische leukemie verbreken de interactie met het micromilieu. Ned. Tijdschr. Hemat. 2013


Bookchapters
1. Trends in Leukemia Research, chapter on CLL; 2005
2. Leerboek immunohematologie, hoofdstuk CLL; 2013
3. Leerboek Hematologie, Hoofdstuk laaggradige lymfomen; 2014

 

 

Research programmes

development of, circumvention of and novel strategies for (development of) chemorefractory CLL

(I) DNA damage response
The DNA damage response axis plays a crucial role in chemoresistance in CLL, as indicated by the prognostic impact of deletions of 17p (locus of TP53) and 11q (locus of ATM). These deletions coincide with mutations in the remaining allele, although frequency, especially for ATM varies. Functional read-outs of the p53 axis are expected to add clinical relevant information on the actual DNA damage response. Currently, different p53 function analyses are being developed. These assays are either based on measurement of (i) RNA expression levels of a single gene (RT-PCRp21) or gene sets (RT-MLPA, currently further developed by us), or protein expression levels (FACSp53-p21) after DNA damage by irradiation or etoposide/nutlin exposition or (ii) gene expression levels at base-line (RT-PCR miR34a). Although all tests relate to p53 function, they provide different information regarding expected responses towards therapy. P53 function assays are of promise in predicting sensitivity to chemotherapeutic agents provided that robustness and clinical applicability is thoroughly studied. In 2011 I started a pilot project within the framework of the European Research initiative on CLL (ERIC) to perform detailed side-by-side analysis of available p53 functional assays in 5 different countries (UK, the Netherlands, Germany, Austria, France, and Czech Republic). This unique collaborative approach will continue the following years and will include (mechanistic) analysis of novel described genetic aberrations in the DNA damage pathway.
(II) Signaling and cross-talk with the microenvironment
In the pathobiology of chronic lymphocytic leukemia (CLL), the tumor microenvironment plays a pivotal role by providing stimuli for survival and proliferation. However, the relevant interactions are still ill-defined and not targeted by current "conventional" treatments. This may explain why, despite major therapeutic advances, B-cell malignancies like CLL still remain incurable. For targeted therapy to succeed, better understanding of the interactions between leukemic cells and their microenvironment is critical. A variety of external signals has been suggested to influence survival of CLL cells, including B cell receptor (BCR) activation, interleukins/chemokines and cellular contact. Yet, these assumptions are predominantly based on in vitro model systems. In the first comparative survey between lymph node (LN) proliferation centers and blood derived CLL cells, we observed striking differences in Bcl-2 family members which correlated with sensitivity to standard chemotherapeutics. Our recent preliminary in vitro data indicate that besides tonic B-cell receptor (BCR) triggering, TNF-receptor family mediated signaling could account for the observed changes. We have also found that besides receptor/ligand interactions, activation of specific kinases by these stimuli hold high promise for targeted intervention. TNF-receptor family ligands CD40L, BAFF and APRIL, purportedly expressed by activated T cells and/or Nurse-like cells in CLL LN, enhance survival at least partly by NF-κB signaling. No study has yet attempted to directly compare CD40L, BAFF and APRIL and the NF-κB signaling involved for their impact on CLL survival and drug sensitivity. In fact, compelling evidence of expression of these ligands in CLL derived LN tissue is lacking. Moreover, no study has yet attempted to dissect pro-survival effects of T cells versus NLC, in relation to TNF(R) and kinase signaling.
In order to turn these concepts into targeted clinical approaches, this program aims to fill the following gaps in knowledge: 1. which signals predominate within the CLL microenvironment to provide chemoresistance and proliferation, 2. what molecular and functional events occur following distinct TNF-receptor family member mediated signaling. 3. Which intracellular signaling pathways hold most promise for therapeutic intervention with emphasis on kinase (family) activation. In order to gather meaningful and clinical relevant results these questions will be addressed by integrated study of LN CLL biopsy specimens, in vitro model systems and in vivo mouse models.
In addition, impact of novel drugs targeting the microenvironment will be addressed by phase 1, 2 and 3 clinical studies in CLL patients of which I am the principal investigator:
- Hovon 109: Lenalidomide in addition to chlorambucil and rituximab for first-line elderly patients; phase 1/2
- Hovon 121: Lenalidomide maintenance following induction treatment in Young/fit patients; phase 3
- Hovon 122: Ofatumumab and CAL101 followed by allo-SCT in refractory patients; phase 2
- LLPC: GS9820 (PI3-kinase inhibitor) for relapsed and refractory CLL and (non-) Hodgkin lymphoma; phase 1
 

Faculty
Prof. dr. A.P. Kater MD PhD

Postdocs
Dr. E. Slinger
Dr. S.H. Tonino MD PhD
Dr. G.J.W. van der Windt

PhD Students
J.A.C. van Bruggen MSc
Z. Chen PhD
M.V. Haselager
T. Hofland MSc
K. Kielbassa
A.C. Leeksma MD
A.W.J. Martens
S. Tahri
Y.J. Thus
I. de Weerdt MD

Others
Drs. J. ter Burg
Dr. J.M.N. Dubois MD
Drs. S. Klein
Drs. R. Liu
D.M.P. Luijks
Drs. S. Terpstra
Drs. C. Wijnands

Prof. dr. E. Eldering (Apoptosis regulation in immuno-hematology)

Prof. dr. M.H.J. van Oers (Pathogenesis and Immunotherapy of B cell malignancies)

Other research related activities
  • Membership of medical or scientific committee, HOVON, CLL
  • Contribution to guidelines and protocols, CLL and MBL treatment
  • Membership of advisory board / Consultant, CEITEC; Central European Institute of Technology, Brno, Czech Republic
  • Membership of advisory board / Consultant, Celgene, Mundipharma
  • Board of directors / Trustees / Supervisory board, Centraal Israelitische ziekenverpleging
  • Membership of editorial board / Editorship, NEDERLANDS TIJDSCHRIFT VOOR HEMATOLOGIE
  • Board of directors / Trustees / Supervisory board, Fonds CIZ/ziekenhuis Amstelland
Current research funding
  • AbbVie B.V.
  • Acerta Pharma B.V.
  • Acerta Pharmaceuticals
  • AMC
  • AMC (Vrijgesteld)
  • AstraZeneca AB R&D Södertälje
  • Celgene International Il Sàrl
  • Genentech Inc.
  • Gilead Sciences, Inc.
  • IQVIA RDS Netherlands B.V.
  • Janssen Cilag B.V.
  • Janssen Research & Development, LLC
  • Johnson & Johnson Shared Services
  • KWF Kankerbestrijding
  • Rijksdienst voor Ondernemend Nederland
  • Stichting AMC Foundation (Vrijgesteld)
  • Stichting Hovon Amsterdam, p/a VUmc
  • ZonMw