WT1 expression at diagnosis does not predict survival in pediatric aml: A report from the Children's Oncology Group

Noronha, Suzie A.; Alonzo, Todd A.; Gerbing, Robert B.; Lacayo, Norman J.; Dahl, Gary V.; Ravindranath, Yaddanapudi; Arceci, Robert J.; Loeb, David M.

doi:10.1002/pbc.22142

Cited by 26 publications

(17 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, although WT1 mutations in AML appear to result in loss of WT1 function, marked overexpression of wild-type WT1 is a common finding in AML. [26][27][28] Further, in one study, patients with pediatric AML with WT1 exon 7 mutations had significantly higher levels of WT1 expression than patients with wild-type WT1. 28 This apparent contradiction, in which a single gene might function as both an oncogene as well as a tumor suppressor, may stem from the ability of the WT1 protein to function either as a transcriptional activator or repressor, depending on a multitude of factors.…”

Section: Discussionmentioning

confidence: 95%

Prevalence and prognostic implications of WT1 mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group

Zeng

Alonzo

et al. 2010

Blood

Self Cite

View full text Add to dashboard Cite

Recent studies of WT1 mutations in acute myeloid leukemia (AML) mostly report an association with unfavorable clinical outcome. We screened 842 patients treated on 3 consecutive pediatric AML trials for WT1 zinc-finger mutations. Eighty-five mutations were detected in 70 of 842 patients (8.3%). Mutations occurred predominantly in exon 7 (n ‫؍‬ 74) but were also found in exons 8 (n ‫؍‬ 5) and 9 (n ‫؍‬ 6).

show abstract

Section: Discussionmentioning

confidence: 95%

Prevalence and prognostic implications of WT1 mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group

Zeng

Alonzo

et al. 2010

Blood

Self Cite

View full text Add to dashboard Cite

show abstract

“…MRD monitoring of WT1 expression levels at the end of treatment has been demonstrated to predict for relapse and death in pediatric AML [32] and may also be helpful for the early detection of relapse [33][34][35]. Despite these and other studies demonstrating the utility of WT1 expression monitoring [29,[36][37][38], controversy still exists with other studies showing no predictive value [39][40][41][42].…”

Section: Wt1 Expression: Mrd Analysis and Immunotherapymentioning

confidence: 98%

The clinical relevance of Wilms Tumour 1 (WT1) gene mutations in acute leukaemia

Fitzgibbon¹,

Paschka

2009

Hematological Oncology

View full text Add to dashboard Cite

Recurrent genetic aberrations are important predictors of outcome in acute myeloid leukaemia (AML). Numerous novel molecular abnormalities have been identified and investigated in recent years adding to the risk stratification and prognostication of conventional karyotyping. Mutations in the Wilms Tumour 1 (WT1) gene were first described more than a decade ago but their clinical significance has only recently been evaluated. WT1 mutations occur in approximately 10% of adult AML patients at diagnosis and are most frequent in the cytogenetically normal (CN) AML subgroup. These mutations appear to confer a negative prognostic outcome by increasing the risk of relapse and death. Mutation frequency is higher in pediatric patients and also appears to confer a negative impact on relapse and survival. Herein, we discuss the importance of WT1 mutations in AML.

show abstract

“…30 Coincidentally occurring translocations, for example, cryptic translocations of t(5;11)(q35;p15.5)/NUP98-NDS1 or mutations such as WT1 or NPM1, can modify the prognostic relevance of the FLT3-ITD. 22,37,58 The prognostic impact of other mutations mentioned in "Diagnostic procedures and initial workup, Molecular genetics" remains unclear. Table 4 proposes genetically defined prognostic groups based on similar data obtained from large studies in Europe and the United States on the prognostic impact of mutations.…”

Section: Molecular Geneticsmentioning

confidence: 99%

Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel

Creutzig

Heuvel‐Eibrink

Gibson

et al. 2012

Blood

474

526

View full text Add to dashboard Cite

IntroductionChildhood acute myeloid leukemia (AML) is a rare and heterogeneous disease, with an incidence of 7 cases per million children younger than 15 years. In high-income countries, intensive therapy in conjunction with effective supportive care has increased survival rates to ϳ 70%. In 1990 and 2003, expert working groups made recommendations for diagnosis, outcomes, standardization of response criteria, and reporting standards for AML. 1,2 Recent improvements in identifying the molecular genetics and pathogenesis of AML have been implemented in the new World Health Organization (WHO) classification of AML. 3 These changes, and the definition of new diagnostic and prognostic markers and their associated targeted therapies, have prompted the update of earlier recommendations by an international group, on behalf of the European LeukemiaNet for AML in adults in 2010. 4 Despite broad overlap in the diagnostic and treatment recommendations for AML for children and adults, there are important differences in both the diagnostic criteria and disease management, which merit age-specific recommendations. The absence of published recommendations specific for pediatric AML motivated an international group of pediatric hematologists and oncologists (panel and participating groups see "Appendix") to develop evidence-and expert opinionbased consensus recommendations for the diagnosis and management of AML in children, incorporating emerging information on the biology of the disease. The scope of the review is presented in the "Appendix." Recommendations for specific subgroups are also included. This article discusses diagnostic procedures and initial workup, prognostic factors, response criteria, and management, and in particular focuses on differences between adults and children with AML. For personal use only. on May 12, 2018. by guest www.bloodjournal.org From WHO classification and pediatric AMLThe recent WHO 2008 classification is applicable to both adult and pediatric AML 3,5 and has been summarized by Döhner et al. 4 The classification contains most, but not all, cytogenetic subgroups specific to children. Differences in genetic background between children and adults are given in Table 1 and discussed further in "Cytogenetics."Compared with previous classifications (European Group of Immunologic Characterization of Leukemias [EGIL], WHO 2001), 6 the new WHO classification introduced a stringently defined subclass of acute leukemias of ambiguous lineage (mixed phenotype acute leukemias [MPALs]), mainly on the basis of detailed immunophenotypic criteria (Table 2) or presence of t(9;22)(q34; q11.2)/BCR-ABL1 or t(v;11q23)/MLL rearrangement. 3,5,6 The new classification aims to create uniform subgroups defined by unifying molecular targets, which allow selection of specific treatment. Diagnostic procedures and initial workupThe minimal diagnostic requirements in childhood AML are morphology with cytochemistry, immunophenotyping, karyotyping, FISH, and specific molecular genetics in the bone marrow, which is comparable ...

show abstract

WT1 expression at diagnosis does not predict survival in pediatric aml: A report from the Children's Oncology Group

Cited by 26 publications

References 19 publications

Prevalence and prognostic implications of WT1 mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group

Prevalence and prognostic implications of WT1 mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group

The clinical relevance of Wilms Tumour 1 (WT1) gene mutations in acute leukaemia

Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel

Contact Info

Product

Resources

About