Human GATA2 mutations and hematologic disease: how many paths to pathogenesis?

Huntington's Disease New Paths to Pathogenesis

Huntington's disease is a progressive autosomal dominant neurodegenerative disorder caused by expansion of a CAG repeat coding for polyglutamine in the huntingtin protein. A recent report suggests a new mechanism involving altered interactions with a protein involved in axonal transport, leading to loss of neurotrophic factor transport. This suggests an intriguing convergence to previously desc...

GATA2 Germline Mutations Impair

GATA factor mutations in hematologic disease.

GATA family proteins play essential roles in development of many cell types, including hematopoietic, cardiac, and endodermal lineages. The first three factors, GATAs 1, 2, and 3, are essential for normal hematopoiesis, and their mutations are responsible for a variety of blood disorders. Acquired and inherited GATA1 mutations contribute to Diamond-Blackfan anemia, acute megakaryoblastic leukem...

How many mutations does it take to make a tumor?

I this issue of PNAS, Stoler and colleagues report that typical sporadic colorectal cancers on average contain at least 11,000 genomic alterations per cell (1). Furthermore, they report that the genomic instability responsible for generating this number of mutations starts very early in the neoplastic process and can be found in adenomatous polyps, which are known to be the precursors of cancer...

Energetics and behavior: many paths to understanding.

In a recent Opinion, Mathot and Dingemanse [1] draw attention to a claimed major assumption of studies linking animal personality and energetics: ‘that the selected measure of [metabolism] is a valid proxy for energetic constraints.’ They argue that unless this assumption is tested, results from many studies are uninterpretable. We would like to argue that the definition of energetic constraint...