Study of Blood Samples From Newborns With Down Syndrome
RATIONALE: Studying the genes expressed in samples of blood from patients with Down syndrome may help doctors identify biomarkers related to cancer.
PURPOSE: This research study is looking at blood samples from newborns with Down syndrome.
Genetic: DNA analysis
Genetic: RNA analysis
Genetic: cytogenetic analysis
Genetic: fluorescence in situ hybridization
Genetic: gene expression analysis
Genetic: microarray analysis
Genetic: mutation analysis
Genetic: polymerase chain reaction
Genetic: polymorphism analysis
Other: flow cytometry
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Observational Model: Case Control
Time Perspective: Prospective
|Official Title:||Biology Study of Transient Myeloproliferative Disorder (TMD) in Children With Down Syndrome (DS)|
- Event-free survival [ Time Frame: length of study ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: length of study ] [ Designated as safety issue: No ]
- Transient myeloproliferative disorder (TMD)-related mortality [ Time Frame: length of study ] [ Designated as safety issue: No ]
- Incidence of subsequent leukemia for patients with resolved TMD [ Time Frame: length of study ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
|Study Start Date:||February 2009|
|Study Completion Date:||May 2016|
|Primary Completion Date:||May 2016 (Final data collection date for primary outcome measure)|
- To further our biological understanding of the natural history of transient myeloproliferative disorder (TMD) and its relationship to subsequent leukemia by facilitating the development of a TMD cell and protein bank, and repository of DNA/RNA from megakaryoblasts for future biological studies.
- To investigate the biology of TMD molecular changes associated with resolution of TMD or its conversion to acute myeloid leukemia within each mortality-risk group by conducting GATA1 mutational analyses, hematopoiesis clonality studies, assessment of RAS mutations, and genomic instability studies using glycophorin A assays.
- To determine if high-resolution microarray genomic analysis of TMD blasts (using Affymetrix SNP Genechip technology to assess gene expression, copy number variation, and loss of heterozygosity) can predict the development of subsequent leukemia.
- To determine the relationship of minimal residual disease (monitored by peripheral blood flow cytometry and GATA1 mutational studies) to clinical remission status and development of subsequent leukemia within each mortality-risk group of TMD patients.
- To evaluate the relationship between karyotype (including FISH analysis) and subsequent leukemia in TMD patients.
- To examine pharmacogenetics and in vitro drug sensitivity to cytarabine (MTT assay) in blasts from TMD patients.
- To examine the relationship of functional polymorphisms in Phase I and Phase II drug detoxification genes, DNA repair, and DNA synthesis pathways that may modify susceptibility to leukemia and outcome in TMD patients.
- To determine the relationship between fibrosis-associated serum factors (e.g., platelet-derived growth factor, transforming growth factor beta, N-terminal peptide of III procollagen, type IV collagen, and hyaluronic acid) and event-free survival.
OUTLINE: This is a multicenter study.
Patients undergo peripheral blood collection periodically for biomarker analysis. Samples are analyzed for GATA1 mutations by real-time PCR, polymorphisms, cytogenetics, - and K-RAS mutations, gene expression, drug sensitivity patterns, and minimal residual disease by flow cytometry.
Patients are followed up periodically for 5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00959283
Show 158 Study Locations
|Principal Investigator:||April D. Sorrell, MD||Beckman Research Institute|