Biology Study of Transient Myeloproliferative Disorder (TMD) in Children With Down Syndrome (DS)
Biology Study of Transient Myeloproliferative Disorder (TMD) in Children With Down Syndrome (DS)
This research study is looking at blood samples from newborns with Down syndrome. Studying the genes expressed in samples of blood from patients with Down syndrome may help doctors identify biomarkers related to cancer.
PRIMARY OBJECTIVES:
I. 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.
II. 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.
III. 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.
IV. 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.
V. To evaluate the relationship between karyotype (including FISH analysis) and subsequent leukemia in TMD patients.
VI. To examine pharmacogenetics and in vitro drug sensitivity to cytarabine (MTT assay) in blasts from TMD patients.
VII. 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.
VIII. 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.
Inclusion Criteria:
Diagnosis of transient myeloproliferative disorder (TMD) at < 90 days of age and meeting 1 of the following criteria:
A diagnosis of Down syndrome or Down syndrome mosaicism AND non-erythroid and non-lymphoid blasts (any amount) in the peripheral blood verified with a second sample
Trisomy 21-positive leukemic blasts documented by biopsy of any organ (including > 5% non-erythroid/non-lymphoid blasts documented by bone marrow aspirate or biopsy)
Institutional immunophenotype characterization is required for study enrollment
Sacramento, California 95817, United States
Denver, Colorado 80218, United States
Minneapolis, Minnesota 55404, United States
New Brunswick, New Jersey 08903, United States
New Hyde Park, New York 11040, United States
New York, New York 10032, United States
Houston, Texas 77030, United States
Spokane, Washington 99204, United States