A practical EPR dosimetry system for routine use in radiotherapy: uncertainty analysis of lithium formate dosimeters at the therapeutic dose level.

In electron paramagnetic resonance (EPR) dosimetry, solid dosimeter materials such as alanine (AL) or, more recently, lithium formate monohydrate (LFM) are typically used. These materials offer high potential for applications in radiotherapy based on their favorable dosimetric properties. Nevertheless, EPR dosimetry is not widespread in the clinics.

c-MYB is a transcriptional regulator of ESPL1/Separase in BCR-ABL-positive chronic myeloid leukemia.

Background: Genomic instability and clonal evolution are hallmarks of progressing chronic myeloid leukemia (CML). Recently, we have shown that clonal evolution and blast crisis correlate with altered expression and activity of Separase, a cysteine endopeptidase that is a mitotic key player in chromosomal segregation and centriole duplication. Hyperactivation of Separase in human hematopoietic cells has been linked to a feedback mechanism that posttranslationally stimulates Separase proteolytic activity after imatinib therapy-induced reduction of Separase protein levels.

The proteolytic activity of separase in BCR-ABL-positive cells is increased by imatinib.

Separase, an endopeptidase required for the separation of sister-chromatides in mitotic anaphase, triggers centriole disengagement during centrosome duplication. In cancer, separase is frequently overexpressed, pointing to a functional role as an aneuploidy promoter associated with centrosomal amplification and genomic instability. Recently, we have shown that centrosomal amplification and subsequent chromosomal aberrations are a hallmark of chronic myeloid leukemia (CML), increasing from chronic phase (CP) toward blast crisis (BC).