R Pieters

..009). We conclude that resistance to l-asparaginase and relapse risk are associated with high expression of AS in TEL-AML1-negative but not TEL-AML1-positive B-lineage ALL...

..This article discusses the factors used in risk stratification and the treatment of pediatric ALL...

..We also did a randomised trial to establish the value of a late intensification course...

..This trial was registered at http://www.controlled-trials.com as no. ISRCTN 75734403...

..This article discusses the factors used in risk stratification and the treatment of pediatric ALL...

..New genetic and epigenetic insights into the biology of MLL-rearranged ALL suggest new possibilities for therapies...

..It is anticipated that genomic research will lead to better classification and to more personalized therapy for individual patients...

..This article provides an overview of available evidence for optimal use of Erwinia asparaginase in the treatment of ALL...

..Further research should explain the role of EVI1+ in disease biology in these cases. Remarkably, no 3q26 abnormalities were identified in EVI1+ pediatric AML...

..8/T6400, also did not modulate Ara-C cytotoxicity. Therefore, we conclude that Ara-C is not a substrate for BCRP and that MDR proteins do not play a significant role in drug resistance in infant ALL...

..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...

..In this study, we provide additional evidence that they should be tested for their efficacy in MLL-rearranged infant ALL in in vivo models...

..GC resistance in childhood ALL cannot be attributed to different mRNA expression levels of the investigated (co)chaperone molecules involved in GC binding and transport to the nucleus...

..Our results suggest that childhood T-ALL is associated with a high expression of DeltaTA-p73. These isoforms may play a role in cellular resistance to DNA-damaging drugs in children at initial diagnosis of T-ALL...

..These data indicate that MRD diagnostics has added value for recognition of risk groups in infant ALL and that MRD diagnostics can be used for treatment intervention in infant ALL as well...

..CONCLUSION: High AML1-TEL expression is an independent poor prognostic factor in t(12;21)+ childhood ALL...

..Aim of this study was to investigate the long-term endocrine effects of treatment of childhood non-Hodgkin lymphoma (NHL)...

..Blood. 2001;97:3605-3611)..

..Impaired motor performance in children who completed treatment for acute lymphoblastic leukemia (ALL) may be related to polymorphisms of the metabolising gene CYP3A5 or vincristine toxicity related genes MDR-1 and MAPT...

..Comparing our data with other studies, we conclude that the prognostic significance for NOTCH1/FBXW7 mutations is not consistent and may depend on the treatment protocol given...

..Together, these findings indicate the importance of the glycolytic pathway in glucocorticoid resistance in ALL and suggest that targeting glycolysis is a viable strategy for modulating prednisolone resistance in ALL...

..CONCLUSIONS: Differential expression of a relatively small number of genes is associated with drug resistance and treatment outcome in childhood ALL...

..05). The association between five coding ATM alterations in T-ALL, their germline presence, white blood cell count and unfavourable outcome may point to a role for ATM in the development of T-ALL in these children...

..These observations imply that suppression of FHIT may be required for the development of MLL, and provide new insights into leukemogenesis and therapeutic possibilities for MLL...

..Although further investigation for the role of BRE in leukemogenesis and outcome is warranted, high BRE expression is an independent prognostic factor for pRFS in pediatric AML...

..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...

..A cluster of abnormalities that contribute to the metabolic syndrome may be expressed at a higher level and therefore result in an increased risk for diabetes mellitus and cardiovascular diseases...

..We showed that both of these genetic abnormalities occur independently from this newly identified 9q34 duplication...

..We conclude that MDR1 expression in -7/7q- AML patients is upregulated at transcriptional, but not at translational level, suggesting that mechanisms other than MDR1 are responsible for the poor prognosis in these patients...

..Therefore, inhibition of aberrant DNA methylation may be an important novel therapeutic strategy for MLL-rearranged ALL in infants...

..This study aims to identify folate-metabolism-related genetic risk factors for low bone mineral density (BMD) during/after pediatric acute lymphoblastic leukemia (ALL) treatment...

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..Therefore, we investigated the frequency of constitutional aberrations in combination with phenotype...

..Given the presented potential of HDAC inhibitors to target important proto-oncogenes including the leukemia-specific MLL fusion in vitro, these agents should urgently be tested in in vivo models and subsequent clinical trials...

..36, P = 0.007). The identification of >1000 miR genes expressed in different types of ALL forms a comprehensive repository for further functional studies that address the role of miRNAs in the biology of ALL...

..78, 95% CI 1.45-23.0; P=0.01) is an independent prognostic factor in DCOG- and COALL-treated t(12;21)-positive ALL...

..05; P=0.001). Neither CRLF2 nor JAK2 were predictors for worse prognosis. If confirmed in prospective series, IKZF1 deletions may be used for risk-group stratification in DS ALL...

..Identification of a potential common leukemogenic NKL downstream pathway will provide a promising subject for future studies...

..However, emerging knowledge about the biology of miRNAs in leukemia may result into a role for these miRNAs in the diagnosis and treatment of acute leukemia...

..To achieve further improvements in outcome, unraveling the biology of MLL-rearranged pediatric AML is warranted...

..In conclusion, we identified new miRNA genes and showed that miRNA expression profiles are ALL subtype-specific rather than linked to the differentiation stadium associated with these subtypes...

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..This may be explained by the rapid removal of apoptotic cells from the circulation in vivo. One additional dose of PEG-asparaginase upfront ALL treatment did not lead to other severe toxicities...

..However, in NPM1 wild-type CN-AML, FLT3/ITD-positive patients had a significantly worse outcome (pEFS 48 vs 18%; P<0.001). We conclude that NPM1 mutations confer a favorable prognosis in childhood AML and in CN-AML in particular...

..This leads to decreased activation of apoptotic parameters in resistant cases of pediatric ALL...

..This trial was registered at www.clinicaltrials.gov as no. NCT 00015873, and at www.controlled-trials.com as no. ISRCTN24251487...

..Biologic characterization of these genes and pathways might elucidate the action of glucocorticoids in ALL cells, possibly suggesting causes of glucocorticoid resistance and new potential targets for therapy...

..We conclude that SET-NUP214 may contribute to the pathogenesis of T-ALL by enforcing T-cell differentiation arrest...

..Screening for these translocation partners is needed for accurate treatment stratification at diagnosis...

..Thus, PKC412-induced apoptosis in infant MLL cells is unlikely to be a consequence of FLT3 inhibition alone but may involve inhibition of multiple other kinases by this drug...

..In conclusion, 6-color FCM significantly improves MRD analysis in ALL but remains less sensitive than PCR-based MRD-diagnostics...

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..We present a pediatric patient with leukemia and a severe, L-asparaginase-induced necrotizing pancreatitis, treated successfully with percutaneous drainage used to flush the infected necrotic parts...

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..Posterior reversible encephalopathy syndrome (PRES) is characterized by seizures, headaches, altered mental status, cortical blindness and typical transient lesions on magnetic resonance imaging...

..The PM adjuvant activity on allergic sensitization is a possible mechanism of action involved, and the induction of airway inflammation is suggested to be of importance in PM-induced adjuvant activity...

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..Ongoing studies should determine whether these neurodegenerative markers in CSF can be used to monitor neuronal and axonal degeneration in these patients during therapy and long-term follow up...

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..Larger studies should be conducted to validate the predictive values of the levels of intact IGFBP-3 and proteolytic fragments in CSF in the follow-up of medulloblastomas...

..25% of precursor B-ALL cases are genetically unclassified and have intermediate prognosis. We aimed to use a genome-wide study to improve prognostic classification of ALL in children...

..SHMT1 1420TT homozygotes only showed decreased MTX sensitivity in the TSI(50, cont). In conclusion, polymorphisms in the folate-related genes MTHFR, MTRR, and SHMT1 are related to MTX resistance in pediatric patients with ALL...

..Most end-of-life decision-making studies have, until now, involved either the general population or newborn infants...

..In conclusion, a more severe decline of anticoagulant and fibrinolytic parameters in children between 11 and 16 years of age underline that these children are at higher risk of thrombosis during ALL induction treatment...

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..The higher incidence of the N363S minor allele and the lower incidence of the ER22/23EK minor allele in our ALL population as compared with a normal population warrants further research...

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..Nevertheless, MRD-based risk group classification can differ between paired BM samples, mainly because of variation below the quantitative range of the PCR assay rather than to a different distribution of leukaemic cells within the BM...

..2-fold increase in ALL risk (P = .001). For the first time, we associate the RFC1 80G>A and NNMT IVS -151C>T variants to an increased ALL susceptibility...

..Here we review the current acquaintance with the biology of infant ALL and describe how this knowledge may lead to innovative therapeutic approaches...

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..The aim of the current study was to explore which microRNA are unique for seven different subtypes of pediatric acute lymphoblastic leukemia...

..In conclusion, OPAL1 expression may not be an independent prognostic feature in childhood ALL, and its previously reported prognostic impact appears to be treatment dependent...

..These gene expression profiles should provide important novel insights in the complex biology of MLL-rearranged infant ALL and boost our progress in finding novel therapeutic solutions...

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..Moreover, it illustrates that although cure of pediatric NLPHL is feasible with chemotherapy only, high dosages of cytotoxic drugs are necessary as salvage treatment in a relatively high proportion of patients after relapse...

..A possible explanation is the mechanism by which Muc2 deficiency may trigger the immune system to release interleukin-10, an anti-inflammatory cytokine before MTX-treatment...

..The t(7;12) is associated with a poor outcome and an ectopic expression of HLXB9 is commonly involved in this genetic subtype of leukemia...

..In this review we will discuss the recent progress that has been made in the use of microarrays for identifying new markers and targets for treatment of acute leukemia in children...

..coli L-asparaginase-treated patients only...

..These data suggest that in response to DOX-induced damage, BMP4 and TCF4 are modulated in such a way that homeostasis of the progenitor compartment is partly preserved...

..The methylation pattern therefore supports a model in which CpG islands are not randomly targeted by methylation in cancer. Specific transcriptional silencing probably marks genes that can become methylated...

..In conclusion, our mouse model may prove a valuable tool to identify genes that cooperate in BCL2-enforced lymphoma/leukemogenesis...

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..The high frequency of immature and oligoclonal Ig/TCR rearrangements is probably caused by early (prenatal) oncogenic transformation in immature B-lineage progenitor cells with germline Ig/TCR genes combined with a short latency period...

..We conclude that mucosal immune responses remain resilient during MTX-induced mucositis. Whereas TNF-alpha production may contribute to mucosal damage, IL-10 may regulate by restricting excessive mucositis...

..Furthermore, we contradict the general thought that leukemic cells specifically lack AS compared with normal bone marrow and blood cells...

..GC resistance in childhood ALL cannot be attributed to an inability of resistant cells to up-regulate the expression of the GR upon GC exposure, nor to differences in GR promoter usage (at baseline and upon GC exposure)...

..051). In conclusion, ALL subtypes have a unique expression pattern of apoptosis genes and our data suggest that selective genes are linked to cellular drug resistance and prognosis in childhood B-lineage ALL...

..Because a sternal mass is often alarming, it is important to identify the clinical features of benign processes...

..We performed a randomized study investigating whether an exercise program could prevent these side effects...

..Long-term writing difficulties in children after treatment with vincristine for acute lymphoblastic leukemia, Wilms tumor, B non-Hodgkin lymphoma, and malignant mesenchymal tumors, were investigated...

..The purpose of this study was to investigate the correlation between plasma renin levels and blood pressure in a larger cohort of WT patients...

..Prospective studies are required to establish the clinical value of TCR Vbeta CDR3 repertoire analysis to predict the clinical response in these patients...

..LMO2 abnormalities represent about 9% (13/138) of pediatric T-ALL cases and are more frequent in pediatric T-ALL than appreciated until now...

..In conclusion, although L-Asp exposure induces the expression of AS mRNA, the up-regulated gene expression does not correlate with an early clinical poor response to this drug in children with ALL...

..In conclusion, low baseline expression of PARP and procaspase-2 is related to cellular drug resistance in childhood acute lymphoblastic leukemia...

..BMAD was normal after CNS-irradiation. CONCLUSIONS: Long term survivors of ALL treated with prednisolone or dexamethasone containing regimens do not differ in height, BMD, or body composition...

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