JCI early table of contents for Feb. 3, 2014

Methylation signature correlates with acute myeloid leukemia survival

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

AUTHOR CONTACT: Ulrich Steidl

Albert Einstein College Of Medicine, Bronx, NY, USA

Phone: (718) 430-3437; E-mail: ulrich.steidl@einstein.yu.edu

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

Phone: 01865-271858; E-mail: frances.platt@pharm.ox.ac.uk

View this article at: http://www.jci.org/articles/view/72835?key=f7c5ebb23ba9074d3e81

ALSO IN THIS ISSUE

TITLE: Angiotensin converting enzyme overexpression in myelomonocytes prevents Alzheimer's-like cognitive decline

AUTHOR CONTACT: Maya Koronyo-Hamaoui

Cedars-Sinai Medical Center, Los Angeles, CA, USA

Phone: 310-423-4607; Fax: 310-423-0302; E-mail: maya.koronyo@cshs.org

View this article at: http://www.jci.org/articles/view/66541?key=1d715a3c7a9b161c199c

TITLE: Mutant p53–associated myosin-X upregulation promotes breast cancer invasion and metastasis

AUTHOR CONTACT: Johanna Ivaska

University Of Turku, Turku, , FIN

Phone: +3587203971; E-mail:johanna.ivaska@utu.fi

View this article at: http://www.jci.org/articles/view/67280?key=d825f4edfaca163d9ebe

TITLE: Hyaluronan digestion controls DC migration from the skin

AUTHOR CONTACT: Richard Gallo

University of California, San Diego School of Medicine, La Jolla, CA, USA

Phone: 8588224608; Fax: 8588226985; E-mail: rgallo@ucsd.edu

View this article at: http://www.jci.org/articles/view/67947?key=ef2368ef66759b5c70fe

TITLE: Chemical chaperone ameliorates pathological protein aggregation in plectin-deficient muscle

AUTHOR CONTACT: Gerhard Wiche

University of Vienna, Vienna, UNK, AUT

Phone: +43 1 4277 52852; Fax: +43 1 42779748; E-mail: gerhard.wiche@univie.ac.at

View this article at: http://www.jci.org/articles/view/71919?key=3b3daaf0908e81205895

TITLE: TSHZ1-dependent gene regulation is essential for olfactory bulb development and olfaction

AUTHOR CONTACT: Ronald J.E. Pennings

Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Phone: +31.24.3617203; Fax: +31.24.3540251; E-mail: r.pennings@kno.umcn.nl

View this article at: http://www.jci.org/articles/view/72466?key=fbe24b6c82fed8a9701c

TITLE: Long-lived intestinal tuft cells serve as colon cancer–initiating cells

AUTHOR CONTACT: Timothy C. Wang

Columbia University College of Physicians and Surgeons, New York, NY, USA

Phone: 212-851-4581; Fax: 212-851-4590; E-mail: tcw21@columbia.edu

View this article at: http://www.jci.org/articles/view/73434?key=61d205245d221e6d4189

Provided by Journal of Clinical Investigation