Acute myeloid leukemia (AML) is characterized by the inappropriate replacement of normal bone marrow with white blood cells due to dysfunctional hematopoietic stem cell (HSC) differentiation. Many of the identified AML-associated mutations lie within genes encoding epigenetic modifiers, suggesting that evaluation of epigenetic signatures could be used to identify sub-groups of AML.
In this issue of the Journal of Clinical Investigation, Ulrich Steidl and colleagues at the Albert Einstein College of Medicine compared methylation profiles between healthy populations of HSCs, myeloid progenitor cells, and red blood cell progenitors to evaluate differences in epigenetic profiles and found that the greatest change in epigenetic signatures occurred when HSCs committed to a differentiation pathway.
The authors developed a metric of methylation patterns associated with HSC cell fate and evaluated methylation patterns in AML patient samples. The methylation profile in patient samples was prognostic for overall survival, regardless of treatment regime or particular mutation.
TITLE: HSC commitment–associated epigenetic signature is prognostic in acute myeloid leukemia
View this article at: http://www.jci.org/articles/view/71264?key=071e25e79465f5af1c7a
Researchers characterize a biomarker for lysosomal storage disorders
Lysosomal storage disorders (LSDs) are a common cause of neurodegenerative disease in young children. These diseases are difficult to diagnosis in the early stages; therefore, it is difficult to develop therapeutic strategies that prevent symptom onset. In this issue of the Journal of Clinical Investigation, Frances M. Platt and colleagues at the University of Oxford devised a method for evaluating the relative volume of acidic compartments as an indicator of LSDs. Using the commercially available pH-indicator dye, Lysotracker, the authors were able to calculate the relative acidic compartment volume in circulating B cells. Use of this metric in samples from young LSD patients revealed that the relative acidic compartment volume correlated with clinical severity, and could be used to evaluate patient response to a particular therapy.
TITLE: Relative acidic compartment volume as a lysosomal storage disorder–associated biomarker
AUTHOR CONTACT: Frances Platt University of Oxford, Oxford, , GBR
View this article at:http://www.jci.org/articles/view/72835?key=f7c5ebb23ba9074d3e81