Cytokine Gene Polymorphisms in Bone Marrow Failure
Condition: Bone Marrow Diseases
MeSH terms: Bone Marrow Failure Disorders; Pancytopenia; Bone Marrow Diseases
Study type: Observational

Summary: 
      This study will examine whether cytokine gene polymorphisms affect the progression or
      response to therapy of bone marrow failure disorders. Cytokine genes instruct cells to
      produce proteins called cytokines that influence immune system response. As with many genes,
      the cytokine genes differ slightly from person to person. These differences are called gene
      polymorphisms. Different patients with the same bone marrow failure disease often progress
      and respond to treatment differently. This study will look at the possible role of cytokine
      gene polymorphisms in these differences.

      Patients between 2 and 80 years old who have participated in an NHLBI Hematology Branch
      treatment protocol for acquired aplastic anemia, myelodysplastic syndrome, or pure red cell
      aplasia are recruited to participate in this study. Blood collected and stored at the time of
      screening for the treatment protocol will be tested for cytokine gene polymorphisms. No
      additional tests, procedures, or treatments are involved in this study.
    

Detailed description: 
      The NHLBI Hematology Branch is investigating features that may affect the clinical course of
      bone marrow failure patients.

      We are particularly interested in identifying factors, which determine treatment response and
      outcome. Cytokines are biological mediators of the immune response. In a normal population
      there is considerable variation in the precise sequence of the genes which control cytokine
      production (Cytokine Gene Polymorphism or CGP). As a consequence individuals differ in the
      quality of the immune response they mount against self or foreign antigens. Since the bone
      marrow failure disorders aplastic anemia and myelodysplastic syndrome involve auto-immune
      suppression of marrow function, it is important to discover whether there are any recurrent
      patterns of cytokine production in these disorders which may contribute to the marrow
      failure. This can be done by studying the sequences of the genes that control cytokine
      production to find out whether there are any recurrent gene patterns in the diseases studied.
      In addition we need to understand why some patients fail to respond to immunosuppressive
      treatments. By comparing CGP in responders and non-responders we may be able to find patterns
      of cytokine production that are favorable or unfavorable for response. Better understanding
      of CGPs in marrow failure syndromes should make it possible to improve the outcome for
      patients who fail immune suppression by using drugs which block specific cytokines.

      None of these polymorphisms are associated with known clinical disease to be classifiable as
      a 'genetic defect'. All testing will be done on samples collected and stored for research
      purposes from consenting bone marrow failure subjects who have or will be participating on
      Hematology Branch research protocols.
    

Observational model: Cohort
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        This is an ancillary study to a primary treatment protocol. Clinical data from the
        treatment protocol will be used in this protocol's analyses. All testing will be done on
        samples collected and stored for research purposes from consenting bone marrow failure
        subjects who have or will be participating on Hematology Branch bone marrow failure
        treatment research protocols.
      
Keywords: Tumor Necrosis Factor Alpha (TNF-Alpha); Interferon-Gamma (IFN-Gamma); Transforming Growth Factor Beta 1 (TGF-B1); Interleukin-10 (IL-10); Interleukin-6 (IL-6)