Study of Blood Samples From Newborns With Down Syndrome

Study ID

Cancer Related

Healthy Volunteers

Study Sites

  • Children’s Medical Center (Dallas, Plano, Southlake)


Principal Investigator

Official Title

Biology Study of Transient Myeloproliferative Disorder (TMD) in Children With Down Syndrome (DS)

Brief Overview

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.



- 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

Patients are followed up periodically for 5 years.

Participant Eligibility


- 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

- Patients with typical physical characteristics of Down syndrome are allowed
before cytogenetic or FISH confirmation of the diagnosis

- Trisomy 21-positive leukemic blasts documented by biopsy of any organ (including
> 5% non-erythroid/non-lymphoid blasts documented by bone marrow aspirate or

- Infants with isolated trisomy 21 positivity identified only in the leukemic
blasts are allowed

- Institutional immunophenotype characterization is required for study enrollment


- Not specified


- Not specified