Unraveling Tumor Growth in Stem Cells

At the University of Cambridge, researchers have discovered that a single mutation in a leukemia-associated gene reduces the ability of blood stem cells to make more blood stem cells, but leaves their progeny daughter cells unaffected.

At the University of Cambridge, researchers have discovered that a single mutation in a leukemia-associated gene reduces the ability of blood stem cells to make more blood stem cells, but leaves their progeny daughter cells unaffected.

Their findings have relevance to all cancers that are suspected to have a stem cell origin as they advance our understanding of how single stem cells are subverted to cause tumors.

Study Sheds Light on How Disease Mutations Affect the Parkin Protein
The crystal structure of Parkin, a protein found in cells that when mutated can lead to a hereditary form of Parkinson's disease, has been determined by researchers.

Published this week in PLOS Biology, the study by Professor Tony Green and his team at the Cambridge Institute for Medical Research is the first to isolate highly purified single stem cells and study their individual responses to a mutation that can predispose individuals to a human malignancy. This mutation is in a gene called JAK2, which is present in most patients with myeloproliferative neoplasms (MPNs)—a group of bone marrow diseases that are characterized by the over-production of mature blood cells and by an increased risk of developing leukemia.

Using a unique mathematical modeling approach, carried out in collaboration with Professor Ben Simons at the Cavendish Laboratory in Cambridge, in combination with experiments on single mouse stem cells, the researchers identified a distinct cellular mechanism that operates in stem cells but not in their daughter cells.

"This study is an excellent example of an inter-disciplinary collaboration pushing the field forward," says lead author Dr David Kent. "Combining mathematical modeling with a large number of single stem cell assays allowed us to predict which cells lose their ability to expand. We were able to reinforce this prediction by testing the daughter cells of single stem cell divisions separately and showing that mutant stem cells more often undergo symmetric division to give rise to two non-stem cells."

Oncogene Mutation Hijacks Splicing Process to Promote Growth: Research
An international team of researchers has found that a singular gene mutation helps brain cancer cells to not just survive, but grow tumors rapidly by altering the splicing of genes that control cellular metabolism.

Characterizing the mechanisms that link JAK2 mutations with this pattern of stem cell division—a pattern that eventually leads to the development of MPNs—will inform our understanding of the earliest stages of tumor establishment and of the competition between tumor stem cells, say the authors. The next step, currently underway at the Cambridge Institute for Medical Research, is to understand the effect that acquiring additional mutations has on blood stem cells, as these are thought to drive the expansion of blood progenitor cells, leading to the eventual transformation to leukemia that occurs in patients with MPNs.

Source-Eurekalert

Rare Genetic Mutations Team Up To Cause Schizophrenia: Family Studies
Researchers at Johns Hopkins have found that individually harmless genetic variations affecting related biochemical processes may team up to increase the risk of schizophrenia.

Research: PARP Inhibitor Shows Activity in Pancreatic, Prostate Cancers Among Patients Carrying BRCA Mutations
The oral drug olaparib was found to be effective against advanced pancreatic and prostate cancers.