Targeted Chemoprevention of Progressive Marrow Failure in Patients with Fanconi Anemia using ...

31 Pages·2013·0.93 MB·English

Targeted Chemoprevention of
Progressive Marrow Failure in
Patients with Fanconi Anemia using
Quercetin, a Pilot study
Parinda Mehta, M.D.
Division of Bone Marrow Transplantation and
Immune Deficiency
Cincinnati Children’s Hospital Medical Center
Treatment options for Fanconi Anemia
Moderate End-stage
Early marrow
Diagnosis
marrow failure Marrow failure
failure
Comprehensive Watchful waiting Newer Radiation-free
Care Clinic Androgens Hematopoietic
Transplantation
Complementation
Need for an effective novel therapy with a better toxicity profile

Reactive Oxygen Species (ROS) in
FA
• Studies in both animals and human subjects
indicate that high levels of and increased
sensitivity to ROS plays an important role in
pathogenesis of bone marrow failure in patients
with FA
ROS
Reactive oxygen species (ROS)
• Reactive oxygen species (ROS) refer to a variety
of molecules and free radicals derived from
molecular oxygen
• The biologically relevant ROS, such as hydrogen
peroxide (H2O2), superoxide (O2), and the
hydroxyl radical (HO), are generated from the
precursor superoxide anion

Consequences of increased
oxidative stress/ROS
• Oxidative stress is detrimental to cells
due to oxidative damage to lipids,
proteins, and DNA
• This leads to a cascade of events that
leads to apoptosis (cell death) or
uncontrolled proliferation
Consequences of increased
oxidative stress/ROS
MDS/Leukemia/
Marrow Failure
other cancers
What can we do about
this?