Working with stem cells isolated from mice, Ruth Scheicher and colleagues at the University of Veterinary Medicine, Vienna have investigated possible differences between leukemic stem cells and the healthy stem cells in the body. They looked in particular at the function of the CDK6 protein, which is known to be involved in controlling the cell cycle. Surprisingly, CDK6 was also found to regulate the activation of hematopoietic and leukemic stem cells, which it does by inhibiting the transcription factor Egr1. Upon loss of CDK6, Egr1 becomes active and prevents stem cells from dividing. In a further twist to the tale, the mechanism operates only when hematopoietic stem cells are stressed, e.g. in leukemia, and not in the normal physiological situation.

Scheicher is quick to note the significance of her finding: “CDK6 is absolutely necessary for leukemic stem cells to induce disease but plays no part in normal hematopoiesis. We thus have a novel opportunity to target leukemia at its origin. Inhibiting CDK6 should attack leukemic stem cells while leaving healthy HSCs unaffected.”

More information: ‘CDK6 as a key regulator of hematopoietic and leukemic stem cell activation’ by Scheicher R, Hoelbl-Kovacic A, Bellutti F, Tigan AS, Prchal-Murphy M, Heller G, Schneckenleithner C, Salazar-Roa M, Zöchbauer-Müller S, Zuber J, Malumbres M, Kollmann K and Sexl V. Blood.www.bloodjournal.org/content/125/1/90.long