Risks for Therapy-Related MDS/AML Project

Project: Therapy-Related Leukemia Following Autologous Transplantation for Lymphoma
Project Leaders: Ravi Bhatia, M.D.; Timothy O’Connor, Ph.D.; Smita Bhatia, M.D.

The specific aims for this project are as follows:

Aim 1: Understand the mechanisms and significance of DNA repair defects in t-MDS/AML

  1. Study functional defects in DNA repair pathways
  2. Investigate protein alterations in pathways that show functional DNA repair defects

Aim 2: Understand the mechanisms and significance of altered telomere regulation in t-MDS/AML

  1. Investigate mechanisms underlying telomere shortening in patients developing t-MDS/AML
  2. Investigate the relationship of telomere alterations to genetic instability in t-MDS/AML

Aim 3: Study the acquisition of chromosomal lesions, and understand their role in t MDS/AML

  1. Study the prevalence and nature of chromosomal lesions during the course of development of t-MDS/AML
  2. Investigate whether patients at risk for t-MDS/AML demonstrate enhanced susceptibility to develop chromosomal lesions after in vitro genotoxic exposures
  3. Investigate whether structural abnormalities in specific chromosomes are associated with telomere shortening on those chromosomes.

Aim 4: Understand the interaction of abnormalities detailed in Aims 1 through 3, with therapeutic exposures and demographic variables in determining risk of t-MDS/AML

  1. Determine the sequence of acquisition of abnormalities in DNA repair, chromosomal lesions, telomere and hematological parameters in the development of t-MDS/AML
  2. Identify sub-groups at increased risk for developing t-MDS/AML after aHCT

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