Vincent H.J. van der Velden, PhD

Velden,-van-der-51x53px Laboratory Specialist Medical Immunology,
 Department of Immunology
 Email contact: v.h.j.vandervelden@erasmusmc.nl

 Leukemia and lymphoma diagnostics (LLD) Research Group

Acute leukemias are malignancies of immature hematopoietic cells. Depending on the type of malignant cells, two main categories of acute leukemia can be distinguished: acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). A further sub-division can be made based on the immunophenotype and genetic abnormalities. Such a subdivision is necessary because the different subgroups have a different clinical course and as a result, a variety of therapeutic approaches are needed.

ALL is most common in young children (1-6 years of age) and the current chemotherapeutic treatment results in a 5-year survival of approximately 85%. For ALL patients on the one hand, it is important to identify patients with a high risk of recurrence of the disease (relapse); these patients may benefit from intensification of treatment. On the other hand, the recognition of patients at low risk of recurrence is important, because these patients may benefit from a reduction of treatment and therefore a lower risk of side effects in the short and long term. Unlike ALL, AML is most common in adults (especially above the age of sixty). Although chemotherapy can induce clinical remission in the majority of patients, most eventually get a relapse, resulting in a 5-year survival rate of only about 40%. It is therefore clear that for this type of leukemia new therapeutic options are needed.

We and others have recently demonstrated that detection of low numbers of leukemic cells during and after treatment, the so-called detection of minimal residual disease (MRD), has a predictive value in acute leukemia. In our laboratory, flow cytometric immunophenotyping, PCR analysis of chromosomal abnormalities and PCR analysis of immunoglobulin (Ig) and T cell receptor (TCR) gene rearrangements are being used to detect MRD in different patient groups. By detecting MRD, the rate at which the leukemic cells disappear can be established and consequently the effectiveness of the treatment and the risk of relapse can be determined. In addition, MRD detection is used to determine the efficacy of new therapies, including antibody-mediated chemotherapy. It also contributes to the understanding of the immunobiology of acute leukemia (eg. Ig / TCR rearrangement patterns in subtypes of leukemia, subclones).

Figure-6-new-50 

Our specific objectives are:

  1. Understand the immunological characteristics of acute leukemia in children. This includes analysis of extramedullary acute leukemia (such as central nervous system and testis) in order to identify markers that are able to predict extramedullary relapses and which might be used as novel therapeutic targets.
  2. Analysis of Minimal Residue disease:
    - Development and standardization of sensitive techniques to assess MRD in patients with acute leukemia. This includes both cellular and molecular methods.
    - Recognition of MRD-based patient groups that may benefit from intensification or reduction of treatment.
  3. Renewing the diagnosis of hematological malignancies by applying the latest technologies and by implementing new opportunities for flow cytometric diagnosis.
  4. The identification of parameters that influence the efficacy of antibody-based therapies in acute leukemia patients.

Figure3-50p 

 Group members

Vincent van der Velden, Groepsleider
Anne Bras, PhD student
Maaike de Bie, Analist
Claudia Brandt-Hagens, Analist
André Bijkerk, Analist
Jolanda Doekharan-van der Sluis, Analist
Patricia Hoogeveen, Analist
Stijn de Jong, Analist
Romana Jugooa, Analist
Jeroen te Marvelde, Analist
Sanne van de Meerendonk, Analist
Rianne Noordijk, Analist
Sjoerd Oude Alink, Analist
Gonnie Paulides, Analist

figure-07 

 

 Selected Publications

(Check for all publications: Van der Velden V in PubMed)

van Dongen JJ, van der Velden VH, Brüggemann M, Orfao A.
Minimal residual disease (MRD) diagnostics in acute lymphoblastic leukemia (ALL): need for sensitive, fast and standardized technologies.
Blood. 2015 May 21. pii: blood-2015-03-580027. [Epub ahead of print] PubMed PMID: 25999452.

Aalbers AM, van den Heuvel-Eibrink MM, Baumann I, Dworzak M, Hasle H, Locatelli F, De Moerloose B, Schmugge M, Mejstrikova E, Nováková M, Zecca M, Zwaan CM, Te Marvelde JG, Langerak AW, van Dongen JJ, Pieters R, Niemeyer CM, van der Velden VH.
Bone marrow immunophenotyping by flow cytometry in refractory cytopenia of childhood.
Haematologica. 2015 Mar;100(3):315-23. doi: 10.3324/haematol.2014.107706. Epub 2014 Nov 25. PubMed PMID: 25425683; PubMed Central PMCID: PMC4349269.

Porwit A, van de Loosdrecht AA, Bettelheim P, Brodersen LE, Burbury K, Cremers E, Della Porta MG, Ireland R, Johansson U, Matarraz S, Ogata K, Orfao A, Preijers F, Psarra K, Subirá D, Valent P, van der Velden VH, Wells D, Westers TM, Kern W,  Béné MC.
Revisiting guidelines for integration of flow cytometry results in the WHO classification of myelodysplastic syndromes-proposal from the International/European LeukemiaNet Working Group for Flow Cytometry in MDS.
Leukemia. 2014 Sep;28(9):1793-8. doi: 10.1038/leu.2014.191. Epub 2014 Jun 12. PubMed PMID: 24919805.

van der Velden VH, Hoogeveen PG, de Ridder D, Schindler-van der Struijk M, van Zelm MC, Sanders M, Karsch D, Beverloo HB, Lam K, Orfao A, Lugtenburg PJ, Böttcher S, van Dongen JJ, Langerak AW, Kappers-Klunne M, van Lom K.
B-cell prolymphocytic leukemia: a specific subgroup of mantle cell lymphoma.
Blood. 2014 Jul 17;124(3):412-9. doi: 10.1182/blood-2013-10-533869. Epub 2014 Jun 2. PubMed PMID: 24891323.

Gröschel S, Sanders MA, Hoogenboezem R, de Wit E, Bouwman BA, Erpelinck C, van der Velden VH, Havermans M, Avellino R, van Lom K, Rombouts EJ, van Duin M, Döhner K, Beverloo HB, Bradner JE, Döhner H, Löwenberg B, Valk PJ, Bindels EM, de Laat W, Delwel R.
A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia.
Cell. 2014 Apr 10;157(2):369-81. doi: 10.1016/j.cell.2014.02.019. Epub 2014 Apr 3. PubMed PMID: 24703711.

van der Velden VH, Noordijk R, Brussee M, Hoogeveen PG, Homburg C, de Haas V,  van der Schoot CE, van Dongen JJ.
Minimal residual disease diagnostics in acute lymphoblastic leukaemia: impact of primer characteristics and size of junctional  regions.
Br J Haematol. 2014 Feb;164(3):451-3. doi: 10.1111/bjh.12621. Epub 2013 Oct 26. PubMed PMID: 24164448.

Terwijn M, van Putten WL, Kelder A, van der Velden VH, Brooimans RA, Pabst T,  Maertens J, Boeckx N, de Greef GE, Valk PJ, Preijers FW, Huijgens PC, Dräger AM,  Schanz U, Jongen-Lavrecic M, Biemond BJ, Passweg JR, van Gelder M, Wijermans P, Graux C, Bargetzi M, Legdeur MC, Kuball J, de Weerdt O, Chalandon Y, Hess U, Verdonck LF, Gratama JW, Oussoren YJ, Scholten WJ, Slomp J, Snel AN, Vekemans MC, Löwenberg B, Ossenkoppele GJ, Schuurhuis GJ.
High prognostic impact of flow cytometric minimal residual disease detection in acute myeloid leukemia: data from the HOVON/SAKK AML 42A study.
J Clin Oncol. 2013 Nov 1;31(31):3889-97. doi:  10.1200/JCO.2012.45.9628. Epub 2013 Sep 23. PubMed PMID: 24062400.

Feller N, van der Velden VH, Brooimans RA, Boeckx N, Preijers F, Kelder A, de  Greef I, Westra G, Te Marvelde JG, Aerts P, Wind H, Leenders M, Gratama JW, Schuurhuis GJ.
Defining consensus leukemia-associated immunophenotypes for detection of minimal residual disease in acute myeloid leukemia in a multicenter
setting.
Blood Cancer J. 2013 Aug 2;3:e129. doi: 10.1038/bcj.2013.27. PubMed PMID: 23912609; PubMed Central PMCID: PMC3763381.

Aalbers AM, van der Velden VH, Yoshimi A, Fischer A, Noellke P, Zwaan CM, Baumann I, Beverloo HB, Dworzak M, Hasle H, Locatelli F, De Moerloose B, Göhring G, Schmugge M, Stary J, Zecca M, Langerak AW, van Dongen JJ, Pieters R, Niemeyer CM, van den Heuvel-Eibrink MM.
The clinical relevance of minor paroxysmal nocturnal hemoglobinuria clones in refractory cytopenia of childhood: a prospective study by EWOG-MDS.
Leukemia. 2014 Jan;28(1):189-92. doi: 10.1038/leu.2013.195. Epub 2013 Jun 28. PubMed PMID: 23807769.

Bras AE, van den Heuvel-Eibrink MM, van der Sluijs-Gelling AJ, Coenen EA, Wind H, Zwaan CM, te Marvelde JG, van der Burg M, Gibson B, Rijneveld AW, de Haas V, van Dongen JJ, van der Velden VH.
No significant prognostic value of normal precursor B-cell regeneration in paediatric acute myeloid leukaemia after induction treatment.
Br J Haematol. 2013 Jun;161(6):861-4. doi: 10.1111/bjh.12329. Epub 2013 Apr 12. PubMed PMID: 23577982.

Aalbers AM, van den Heuvel-Eibrink MM, de Haas V, Te Marvelde JG, de Jong AX, van der Burg M, Dworzak M, Hasle H, Locatelli F, De Moerloose B, Schmugge M, Stary J, Zecca M, Zwaan CM, van de Loosdrecht AA, van Dongen JJ, Niemeyer CM, van der Velden VH.
Applicability of a reproducible flow cytometry scoring system in the diagnosis of refractory cytopenia of childhood.
Leukemia. 2013 Sep;27(9):1923-5. doi: 10.1038/leu.2013.81. Epub 2013 Mar 15. PubMed PMID: 23493026.

Kalina T, Flores-Montero J, van der Velden VH, Martin-Ayuso M, Böttcher S, Ritgen M, Almeida J, Lhermitte L, Asnafi V, Mendonça A, de Tute R, Cullen M, Sedek L, Vidriales MB, Pérez JJ, te Marvelde JG, Mejstrikova E, Hrusak O, Szczepanski T, van Dongen JJ, Orfao A; EuroFlow Consortium (EU-FP6, LSHB-CT-2006-018708).
EuroFlow standardization of flow cytometer instrument settings and immunophenotyping protocols.
Leukemia. 2012 Sep;26(9):1986-2010. doi: 10.1038/leu.2012.122. Review. PubMed PMID: 22948490; PubMed Central PMCID: PMC3437409.

Dekking EH, van der Velden VH, Varro R, Wai H, Böttcher S, Kneba M, Sonneveld E, Koning A, Boeckx N, Van Poecke N, Lucio P, Mendonça A, Sedek L, Szczepanski T, Kalina T, Kanderová V, Hoogeveen P, Flores-Montero J, Chillón MC, Orfao A, Almeida J, Evans P, Cullen M, Noordijk AL, Vermeulen PM, de Man MT, Dixon EP, Comans-Bitter WM, van Dongen JJ; EuroFlow Consortium (EU-FP6, LSHB-CT-2006-018708).
Flow cytometric immunobead assay for fast and easy detection of PML-RARA fusion proteins for the diagnosis of acute promyelocytic leukemia.
Leukemia. 2012 Sep;26(9):1976-85. doi: 10.1038/leu.2012.125. Epub 2012 May 8. PubMed PMID: 22948489; PubMed Central PMCID: PMC3437408.

Denys B, van der Sluijs-Gelling AJ, Homburg C, van der Schoot CE, de Haas V, Philippé J, Pieters R, van Dongen JJ, van der Velden VH.
Improved flow cytometric detection of minimal residual disease in childhood acute lymphoblastic leukemia.
Leukemia. 2013 Mar;27(3):635-41. doi: 10.1038/leu.2012.231. Epub 2012 Aug 16. PubMed PMID: 22945774.

van Dongen JJ, Lhermitte L, Böttcher S, Almeida J, van der Velden VH, Flores-Montero J, Rawstron A, Asnafi V, Lécrevisse Q, Lucio P, Mejstrikova E, Szczepanski T, Kalina T, de Tute R, Brüggemann M, Sedek L, Cullen M, Langerak AW, Mendonça A, Macintyre E, Martin-Ayuso M, Hrusak O, Vidriales MB, Orfao A; EuroFlow Consortium (EU-FP6, LSHB-CT-2006-018708).
EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes.
Leukemia. 2012 Sep;26(9):1908-75. doi: 10.1038/leu.2012.120. Epub 2012 May 3. PubMed PMID: 22552007; PubMed Central PMCID: PMC3437410.

Jager E, van der Velden VH, te Marvelde JG, Walter RB, Agur Z, Vainstein V.
Targeted drug delivery by gemtuzumab ozogamicin: mechanism-based mathematical model for treatment strategy improvement and therapy individualization.
PLoS One. 2011;6(9):e24265. doi: 10.1371/journal.pone.0024265. Epub 2011 Sep 7. PubMed PMID: 21915304; PubMed Central PMCID: PMC3168467.

de Vries JF, Zwaan CM, De Bie M, Voerman JS, den Boer ML, van Dongen JJ, van der Velden VH.
The novel calicheamicin-conjugated CD22 antibody inotuzumab ozogamicin (CMC-544) effectively kills primary pediatric acute lymphoblastic leukemia cells.
Leukemia. 2012 Feb;26(2):255-64. doi: 10.1038/leu.2011.206. Epub  2011 Aug 26. PubMed PMID: 21869836.