E R van Wering

Publications (166)1090.23 Total impact

• Article: Ontwikkelingen in de diagnostiek en behandeling van leukemie bij kinderen met downsyndroom

  M. Blink, T. D. Buitenkamp, J. P. van Wouwe, E. R. van Wering, V. H. J. van der Velden, C. M. Zwaan
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  ABSTRACT: Kinderen met downsyndroom (DS) hebben een verhoogde kans op zowel acute myeloïde als acute lymfatische leukemie. Deze leukemieën verschillen in klinische karakteristieken en biologische eigenschappen vergeleken met leukemie bij kinderen zonder DS. Tevens hebben kinderen met DS een verhoogde kans op bijwerkingen van cytostatica, wat de behandeling bemoeilijkt. Myeloïde leukemie bij kinderen met DS (ML-DS) is een aparte ziekte-entiteit met specifieke kenmerken. Deze leukemiecellen zijn relatief gevoelig voor chemotherapie, wat dosisreductie mogelijk maakt. Dit leidt ook tot vermindering van toxiciteit, resulterend in een betere overleving vergeleken met kinderen met myeloïde leukemie zonder DS. Daarom is recentelijk een specifiek Europees behandelprotocol voor kinderen met ML-DS ontwikkeld. ML-DS kan voorafgegaan worden door een preleukemische ziektefase op zuigelingenleeftijd, ook wel transiënte leukemie genoemd (TL). TL gaat meestal spontaan in remissie, maar in geval van ernstige symptomatologie is behandeling noodzakelijk. Twintig procent van de TL-patiënten ontwikkelt myeloïde leukemie. Om de behandeling en overleving van kinderen met TL te verbeteren, en om te bestuderen of transitie naar ML-DS voorkomen kan worden met tijdige behandeling van TL, is in Nederland recent een studie- en behandelprotocol gestart. DSALL- patiënten hebben in tegenstelling tot ML-DS-patiënten geen betere prognose dan ALL-patiënten zonder DS. Ook bij DS-ALL verschillen de biologische karakteristieken van non-DS-ALL, maar de leukemische blasten zijn niet gevoeliger voor chemotherapie, zodat dosisreductie niet standaard wordt toegepast. Omdat DS-ALL-patiënten meer toxiciteit ervaren in het huidige SKION-ALL10-behandelprotocol, zijn aanpassingen in de behandeling van DS-ALL-kinderen doorgevoerd. Children with Down syndrome (DS) have an increased risk for developing both acute myeloid as well as acute lymphoblastic leukemia. These leukemias differ in clinical characteristics and biology compared to leukemias in non-DS children. Moreover, children with DS have an increased risk of side-effects from cytostatic therapy, which complicates their treatment. Myeloid leukemia in children with DS (ML-DS) is a unique disease entity. ML-DS blasts are relatively sensitive to chemotherapy, which enables dosereductions. This also leads to a decrease in toxicity; together resulting in improved outcome compared to AML in non-DS children. Therefore, a European treatment protocol specifically for MLDS was recently implemented. ML-DS is often preceded by a preleukemic clone in newborns (transient leukemia: TL), which in most cases resolves spontaneously. However, in case of severe symptoms treatment is indicated. Twenty percent of TL patients subsequently develop myeloid leukemia. To improve treatment and survival of children with TL, and to study if transition to ML-DS canbe prevented by early treatment in the TL phase, a nation-wide TL surveillance and treatment protocol has been opened in the Netherlands recently. The prognosis of DS-ALL patients is at best similar to non-DS-ALL patients. The biological characteristics of leukemic lymphoblasts differ between DS-ALL and non-DS-ALL. DS-ALL lymphoblasts do not have increased sensitivity to chemotherapy compared to non-DS lymphoblasts. Therefore dose-reduction should only be considered in case of unacceptable toxicity. Recent findings suggest that DS-ALL patients experience excessive toxicity during the current DCOG ALL10-protocol. Hence, adjustments in the treatment protocol for DS-ALL patients were made.
  Tijdschrift voor kindergeneeskunde 04/2012; 77(2):52-58.
• Article: Clinical significance of flowcytometric minimal residual disease detection in pediatric acute myeloid leukemia patients treated according to the DCOG ANLL97/MRC AML12 protocol.

  V H J van der Velden, A van der Sluijs-Geling, B E S Gibson, J G te Marvelde, P G Hoogeveen, W C J Hop, K Wheatley, M B Bierings, G J Schuurhuis, S S N de Graaf, E R van Wering, J J M van Dongen
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  ABSTRACT: Analysis of minimal residual disease (MRD) in childhood acute myeloid leukemia (AML) may predict for clinical outcome. MRD levels were assessed by flowcytometric immunophenotyping in 94 children with AML enrolled into a single trial (United Kingdom Medical Research Council AML12 and similar Dutch Childhood Oncology Group ANLL97). An aberrant immunophenotype could be detected in 94% of patients. MRD levels after the first course of chemotherapy predicted for clinical outcome: 3-year relapse-free survival was 85%+/-8% (s.e.) for MRD-negative patients (MRD<0.1%), 64%+/-10% for MRD-low-positive patients (0.1%<or=MRD<0.5%) and only 14+/-9% for MRD-high-positive patients (MRD>or=0.5%; P<0.001), whereas overall survival was 95%+/-5%, 70%+/-10% and 40%+/-13%, respectively, (P<0.001). Multivariate analysis allowing for age, karyotype, FLT3-internal tandem duplications and white blood cell count at diagnosis showed that MRD after the first course of chemotherapy was an independent prognostic factor. Although comparison of paired diagnosis-relapse samples (n=23) showed immunophenotypic shifts in 91% of cases, this did not hamper MRD analysis. In conclusion, flowcytometric MRD detection is possible in children with AML. The level of MRD after the first course of chemotherapy provides prognostic information that may be used to guide therapy.
  Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 09/2010; 24(9):1599-606. · 8.30 Impact Factor
• Article: Preemptive alloimmune intervention in high-risk pediatric acute lymphoblastic leukemia patients guided by minimal residual disease level before stem cell transplantation.

  A C Lankester, M B Bierings, E R van Wering, A J M Wijkhuijs, R A de Weger, J T Wijnen, J M Vossen, B Versluys, R M Egeler, M J D van Tol, H Putter, T Révész, J J M van Dongen, V H J van der Velden, M W Schilham
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  ABSTRACT: Relapse of pediatric acute lymphoblastic leukemia (ALL) remains the main cause of treatment failure after allogeneic stem cell transplantation (alloSCT). A high level of minimal residual disease (MRD) before alloSCT has been shown to predict these relapses. Patients at risk might benefit from a preemptive alloimmune intervention. In this first prospective, MRD-guided intervention study, 48 patients were stratified according to pre-SCT MRD level. Eighteen children with MRD level >or=1 x 10(-4) were eligible for intervention, consisting of early cyclosporine A tapering followed by consecutive, incremental donor lymphocyte infusions (n=1-4). The intervention was associated with graft versus host disease >or=grade II in only 23% of patients. Event-free survival in the intervention group was 19%. However, in contrast with the usual early recurrence of leukemia, relapses were delayed up to 3 years after SCT. In addition, several relapses presented at unusual extramedullary sites suggesting that the immune intervention may have altered the pattern of leukemia recurrence. In 8 out of 11 evaluable patients, relapse was preceded by MRD recurrence (median 9 weeks, range 0-30). We conclude that in children with high-risk ALL, immunotherapy-based regimens after SCT are feasible and may need to be further intensified to achieve total eradication of residual leukemic cells.
  Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 08/2010; 24(8):1462-9. · 8.30 Impact Factor
• Article: EVI1 overexpression in distinct subtypes of pediatric acute myeloid leukemia.

  B V Balgobind, S Lugthart, I H Hollink, S T J C M Arentsen-Peters, E R van Wering, S S N de Graaf, D Reinhardt, U Creutzig, G J L Kaspers, E S J M de Bont, J Stary, J Trka, M Zimmermann, H B Beverloo, R Pieters, R Delwel, C M Zwaan, M M van den Heuvel-Eibrink
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  ABSTRACT: Overexpression of the ecotropic virus integration-1 (EVI1) gene (EVI1+), localized at chromosome 3q26, is associated with adverse outcome in adult acute myeloid leukemia (AML). In pediatric AML, 3q26 abnormalities are rare, and the role of EVI1 is unknown. We studied 228 pediatric AML samples for EVI1+ using gene expression profiling and RQ-PCR. EVI1+ was found in 20/213 (9%) of children with de novo AML, and in 4/8 with secondary AML. It was predominantly found in MLL-rearranged AML (13/47), monosomy 7 (2/3), or FAB M6/7 (6/10), and mutually exclusive with core-binding factor AML, t(15;17), and NPM1 mutations. Fluorescent in situ hybridization (FISH) was performed to detect cryptic 3q26 abnormalities. However, none of the EVI1+ patients harbored structural 3q26 alterations. Although significant differences in 4 years pEFS for EVI1+ and EVI1- pediatric AML were observed (28%+/-11 vs 44%+/-4, P=0.04), multivariate analysis did not identify EVI1+ as an independent prognostic factor. We conclude that EVI1+ can be found in approximately 10% of pediatric AML. Although EVI1+ was not an independent prognostic factor, it was predominantly found in subtypes of pediatric AML that are related with an intermediate to unfavorable prognosis. Further research should explain the role of EVI1+ in disease biology in these cases. Remarkably, no 3q26 abnormalities were identified in EVI1+ pediatric AML.
  Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 04/2010; 24(5):942-9. · 8.30 Impact Factor
• Article: Genome-wide expression analysis of paired diagnosis-relapse samples in ALL indicates involvement of pathways related to DNA replication, cell cycle and DNA repair, independent of immune phenotype.

  F J T Staal, D de Ridder, T Szczepanski, T Schonewille, E C E van der Linden, E R van Wering, V H J van der Velden, J J M van Dongen
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  ABSTRACT: Almost a quarter of pediatric patients with acute lymphoblastic leukemia (ALL) suffer from relapses. The biological mechanisms underlying therapy response and development of relapses have remained unclear. In an attempt to better understand this phenomenon, we have analyzed 41 matched diagnosis-relapse pairs of ALL patients using genome-wide expression arrays (82 arrays) on purified leukemic cells. In roughly half of the patients, very few differences between diagnosis and relapse samples were found ('stable group'), suggesting that mostly extra-leukemic factors (for example, drug distribution, drug metabolism, compliance) contributed to the relapse. Therefore, we focused our further analysis on 20 sample pairs with clear differences in gene expression ('skewed group'), reasoning that these would allow us to better study the biological mechanisms underlying relapsed ALL. After finding the differences between diagnosis and relapse pairs in this group, we identified four major gene clusters corresponding to several pathways associated with changes in cell cycle, DNA replication, recombination and repair, as well as B-cell developmental genes. We also identified cancer genes commonly associated with colon carcinomas and ubiquitination to be upregulated in relapsed ALL. Thus, about half of the relapses are due to the selection or emergence of a clone with deregulated expression of genes involved in pathways that regulate B-cell signaling, development, cell cycle, cellular division and replication.
  Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 03/2010; 24(3):491-9. · 8.30 Impact Factor
• Article: Frequent Instability of Type I and H Aberrations Between Diagnosis and Relapse Observed in Pediatric Aml; Implications for Targeted Therapy and MRD Detection

  C. Bachas, G.J. Schuurhuis, I.H.I.M. Hollink, B.F. Goemans, D. Reinhardt, C.M. Zwaan, M.M. van den Heuvel, E.S.J.M. De Bont, E.R. van Wering, G. Kaspers, J. Cloos
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  ABSTRACT: Times Cited: 1 Meeting Abstract English Cited References Count: 0 532DS 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA WASHINGTON
  Blood 11/2009; 114(22):649-650. · 9.90 Impact Factor
• Article: Low Frequency of MLL-PTD Detected in Pediatric Acute Myeloid Leukemia Using MLPA Screening

  B. Balgobind, I.H.I.M. Hollink, D. Reinhardt, E.R. van Wering, S.S.N. de Graaf, A. Baruchel, J.M. Cayuela, R. Pieters, C.M. Zwaan, M.M. Heuvel-Eibrink
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  ABSTRACT: Times Cited: 0 Meeting Abstract English Cited References Count: 0 389OP 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA WASHINGTON
  Blood 11/2008; 112(11):538. · 9.90 Impact Factor
• Article: EVI1 Overexpression in Pediatric Acute Myeloid Leukemia Associated with Unfavorable Subtypes

  B.V. Balgobind, S. Lugthart, I.H.I.M. Hollink, S.T.J.C. Arentsen-Peters, E.R. van Wering, S.S.N. de Graaf, D. Reinhardt, G. Kaspers, J. Stary, J. Trka, M. Zimmermann, R. Delwel, R. Pieters, C.M. Zwaan, M.M. Heuvel-Eibrink
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  ABSTRACT: Times Cited: 0 Meeting Abstract English Cited References Count: 0 389OP 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA WASHINGTON
  Blood 11/2008; 112(11):636. · 9.90 Impact Factor
• Article: Identification of Gene Expression Signatures Accurately Predicting Cytogenetic Subtypes in Pediatric Acute Myeloid Leukemia

  B.V. Balgobind, M.M. Heuvel-Eibrink, R.X. Menezes, D. Reinhardt, I.H.I.M. Hollink, S.T.J.C. Arentsen-Peters, E.R. van Wering, G. Kaspers, J. Cloos, E.S.J.M. De Bont, A. Baruchel, J.M. Cayuela, J. Staty, J. Trka, B. Beverloo, R. Pieters, C.M. Zwaan, M.L. den Boer
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  ABSTRACT: Times Cited: 0 Meeting Abstract English Cited References Count: 0 389OP 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA WASHINGTON
  Blood 11/2008; 112(11):537. · 9.90 Impact Factor
• Article: Monoallelic or biallelic LMO2 expression in relation to the LMO2 rearrangement status in pediatric T-cell acute lymphoblastic leukemia.

  P Van Vlierberghe, H B Beverloo, J Buijs-Gladdines, E R van Wering, M Horstmann, R Pieters, J P P Meijerink
  Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 08/2008; 22(7):1434-7. · 8.30 Impact Factor
• Article: BMI1 as oncogenic candidate in a novel TCRB-associated chromosomal aberration in a patient with TCRgammadelta+ T-cell acute lymphoblastic leukemia.

  N S D Larmonie, W A Dik, H B Beverloo, E R van Wering, J J M van Dongen, A W Langerak
  Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 07/2008; 22(6):1266-7. · 8.30 Impact Factor
• Article: T-cell receptor Vbeta CDR3 oligoclonality frequently occurs in childhood refractory cytopenia (MDS-RC) and severe aplastic anemia.

  A C H de Vries, A W Langerak, B Verhaaf, C M Niemeyer, J Stary, K Schmiegelow, E R van Wering, C M Zwaan, A Beishuizen, R Pieters, M M van den Heuvel-Eibrink
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  ABSTRACT: (Very) severe acquired aplastic anemia ((v)SAA) and myelodysplastic syndrome (MDS) are rare diseases in childhood. (V)SAA is a bone marrow (BM) failure syndrome characterized by immune-mediated destruction of hematopoietic progenitors. MDS is a malignant clonal stem cell disorder, of which the hypoplastic variant is, in case of absence of a cytogenetic clone, difficult to separate from (v)SAA. Recently, studies provided a molecular signature of autoimmunity in adult (v)SAA, by showing oligoclonality based on the length of the TCR Vbeta CDR3 region. We investigated retrospectively the frequency and the discriminative value of TCR Vbeta CDR3 oligoclonality in pediatric (v)SAA and MDS patients. Peripheral blood (PB) and/or BM mononuclear cell samples of pediatric patients with (v)SAA (n=38), refractory cytopenia (MDS-RC) (n=28) and 18 controls were analysed via TCR Vbeta heteroduplex PCR analysis of extracted RNA. A skewed TCR Vbeta CDR3 repertoire was found in 21/38 (v)SAA and in 17/28 RC patients in contrast to 2/18 in the control group. These data suggest an overlapping group of RC and SAA patients that may share a common immune-mediated pathogenesis. Prospective studies are required to establish the clinical value of TCR Vbeta CDR3 repertoire analysis to predict the clinical response in these patients.
  Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 07/2008; 22(6):1170-4. · 8.30 Impact Factor
• Article: Cooperative genetic defects in TLX3 rearranged pediatric T-ALL.

  P Van Vlierberghe, I Homminga, L Zuurbier, J Gladdines-Buijs, E R van Wering, M Horstmann, H B Beverloo, R Pieters, J P P Meijerink
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  ABSTRACT: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive neoplastic disorder, in which multiple genetic abnormalities cooperate in the malignant transformation of thymocytes. About 20% of pediatric T-ALL cases are characterized by TLX3 expression due to a cryptic translocation t(5;14)(q35;q32). Although a number of collaborating genetic events have been identified in TLX3 rearranged T-ALL patients (NOTCH1 mutations, p15/p16 deletions, NUP214-ABL1 amplifications), further elucidation of additional genetic lesions could provide a better understanding of the pathogenesis of this specific T-ALL subtype. In this study, we used array-CGH to screen TLX3 rearranged T-ALL patients for new chromosomal imbalances. Array-CGH analysis revealed five recurrent genomic deletions in TLX3 rearranged T-ALL, including del(1)(p36.31), del(5)(q35), del(13)(q14.3), del(16)(q22.1) and del(19)(p13.2). From these, the cryptic deletion, del(5)(q35), was exclusively identified in about 25% of TLX3 rearranged T-ALL cases. In addition, 19 other genetic lesions were detected once in TLX3 rearranged T-ALL cases, including a cryptic WT1 deletion and a deletion covering the FBXW7 gene, an U3-ubiquitin ligase that mediates the degradation of NOTCH1, MYC, JUN and CyclinE. This study provides a genome-wide overview of copy number changes in TLX3 rearranged T-ALL and offers great new challenges for the identification of new target genes that may play a role in the pathogenesis of T-ALL.
  Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 05/2008; 22(4):762-70. · 8.30 Impact Factor
• Article: Classification of paediatric acute myeloid leukaemia utilizing gene expression profiling

  B.V. Balgobind, M.M. Heuvel-Eibrink, R.X. Menezes, D. Reinhardt, I.H.I.M. Hollink, T.J.C.M. Peters, E.R. van Wering, G.J.L. Kaspers, J. Cloos, E.S.J.M. Bont, J. Cayuela, A. Baruchel, J. Trka, J. Stary, R. Pieters, C.M. Zwaan, M.L. den Boer
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  ABSTRACT: Times Cited: 0 Meeting Abstract English 285 Cited References Count: 0 289CL 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND OXFORD Suppl. 1
  British Journal of Haematology 04/2008; 141:105. · 4.94 Impact Factor
• Article: NF1 microdeletion in paediatric MLL rearranged AML and T-ALL: a novel mechanism for RAS activation

  B.V. Balgobind, P. Van Viierberghe, A.M.W. van den Ouweland, H.B. Beverloo, J.N.R. Terlouw-Kromosoeto, E.R. van Wering, G.J.L. Kaspers, D. Reinhardt, M. Horstmann, R. Pieters, C.M. Zwaan, M.M. Heuvel-Eibrink, J.P.P. Meijerink
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  ABSTRACT: Times Cited: 0 Meeting Abstract English 281 Cited References Count: 0 289CL 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND OXFORD Suppl. 1
  British Journal of Haematology 04/2008; 141:103-104. · 4.94 Impact Factor
• Article: Quality assessment of immunological marker analysis and the immunological diagnosis in leukaemia and lymphoma: a multi‐centre study

  M. B. Van't Veer, J. C. Kluin‐Nelemans, C. E. Van Der Schoot, W. L. J. Van putten, H. J. Adriaansen, E. R. Van Wering
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  ABSTRACT: Summary In order to standardize and assess the quality of immunophenotyping of leukaemias and lymphomas for diagnostic purposes, a cooperative study group in the Netherlands, SIHON, has formulated guidelines for the composition of antibody panels to be applied and guidelines for the interpretation of the marker analysis. To assess the value of these guidelines frozen cell samples of three patients with different haematological malignancies were sent to the 26 participating laboratories twice a year. Here we present the results with respect to the marker analysis and to the immunological diagnosis on 387 samples from 18 patients. A large inter-laboratory variation was seen in the percentage of positive cells for each marker, which influenced the valuation of a marker to be discordant positive in up to 23% and discordant negative in up to 40%. No single major factor could be traced to explain the large variation in the results. However, probably due to the balanced composition of the antibody panel and to the application of the guidelines for interpretation, this variation did not much influence the agreement in immunological diagnosis. In only 13/387 samples (3.3%) differences in the percentage of positive cells caused disagreement in the final diagnosis. In 23 samples (5.9%) the disagreement was due to an incorrect application of the guidelines. Quantitative data of single observations obtained from different laboratories, in which the materials and methods are not standardized, cannot be compared; but standardization of guidelines for marker sets and for interpretation contributes to a high grade of agreement in immunological diagnosis.
  British Journal of Haematology 03/2008; 80(4):458 - 465. · 4.94 Impact Factor
• Article: Classification of pediatric acute myeloid leukemia utilizing gene expression profiling

  B.V. Balgobind, M.M. Heuvel-Eibrink, R.X. Menezes, D. Reinhardt, I.H.I.M. Hollink, T.J.C.M. Peters, E.R. van Wering, G.J.L. Kaspers, J. Cloos, E. de Bont, J. Cayuela, A. Baruchel, J. Trka, J. Stary, R. Pieters, C.M. Zwaan, M.L. den Boer
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  ABSTRACT: Times Cited: 0 Meeting Abstract English Cited References Count: 0 265QD 233 SPRING STREET, NEW YORK, NY 10013 USA NEW YORK Suppl. 1
  Annals of Hematology 02/2008; 87:S1. · 2.62 Impact Factor
• Article: NF1 microdeletions in pediatric MLL-rearranged AML: A novel mechanism for ras activation

  B.V. Balgobind, P. Van Vlierberghe, I. Hollink, A.M.W. van den Ouweland, H.B. Beverloo, J.N.R. Terlouw-Kromosoeto, E.R. van Wering, G.J.L. Kaspers, D. Reinhardt, M. Horstmann, K. Hahlen, R. Pieters, C.M. Zwaan, J.P.P. Meijerink, M.M. Heuvel-Eibrink
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  ABSTRACT: Times Cited: 0 Meeting Abstract English Cited References Count: 0 265QD 233 SPRING STREET, NEW YORK, NY 10013 USA NEW YORK Suppl. 1
  Annals of Hematology 02/2008; 87:S12. · 2.62 Impact Factor
• Article: Prognostic significance of molecular-cytogenetic abnormalities in pediatric T-ALL is not explained by immunophenotypic differences.

  M van Grotel, J P P Meijerink, E R van Wering, A W Langerak, H B Beverloo, J G C A M Buijs-Gladdines, N B Burger, M Passier, E M van Lieshout, W A Kamps, A J P Veerman, M M van Noesel, R Pieters
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  ABSTRACT: Pediatric T-cell acute lymphoblastic leukemia (T-ALL) is characterized by chromosomal rearrangements possibly enforcing arrest at specific development stages. We studied the relationship between molecular-cytogenetic abnormalities and T-cell development stage to investigate whether arrest at specific stages can explain the prognostic significance of specific abnormalities. We extensively studied 72 pediatric T-ALL cases for genetic abnormalities and expression of transcription factors, NOTCH1 mutations and expression of specific CD markers. HOX11 cases were CD1 positive consistent with a cortical stage, but as 4/5 cases lacked cytoplasmatic-beta expression, developmental arrest may precede beta-selection. HOX11L2 was especially confined to immature and pre-AB developmental stages, but 3/17 HOX11L2 mature cases were restricted to the gammadelta-lineage. TAL1 rearrangements were restricted to the alphabeta-lineage with most cases being TCR-alphabeta positive. NOTCH1 mutations were present in all molecular-cytogenetic subgroups without restriction to a specific developmental stage. CALM-AF10 was associated with early relapse. TAL1 or HOX11L2 rearrangements were associated with trends to good and poor outcomes, respectively. Also cases with high vs low TAL1 expression levels demonstrated a trend toward good outcome. Most cases with lower TAL1 levels were HOX11L2 or CALM-AF10 positive. NOTCH1 mutations did not predict for outcome. Classification into T-cell developmental subgroups was not predictive for outcome.
  Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 02/2008; 22(1):124-31. · 8.30 Impact Factor
• Article: NF1 microdeletions in pediatric MLL-rearranged AME and T-ALL: A noyel mechanism for RAS activation

  B.V. Balgobind, P. Van Vlierberghe, I.H. Hollink, A.M.W. den Ouweland, H.B. Beverloo, J.N.R. Terlouw-Kromosoeto, E.R. van Wering, G.J.L. Kaspers, D. Reinhardt, M. Horstmann, K. Hahlen, R. Pieters, C.M. Zwaan, J.P.P. Meijerink, M.M. Heuvel-Eibrink
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  ABSTRACT: Times Cited: 0 Meeting Abstract English 757 Cited References Count: 0 233OS 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA WASHINGTON Part 1
  Blood 11/2007; 110(11):233A. · 9.90 Impact Factor