Runx1 Loss Minimally Impacts Long-Term Hematopoietic Stem Cells

RUNX1 encodes a DNA binding subunit of the core-binding transcription factors and is frequently mutated in acute leukemia, therapy-related leukemia, myelodysplastic syndrome, and chronic myelomonocytic leukemia. Mutations in RUNX1 are thought to confer upon hematopoietic stem cells (HSCs) a pre-leukemic state, but the fundamental properties of Runx1 deficient pre-leukemic HSCs are not well defined. Here we show that Runx1 deficiency decreases both apoptosis and proliferation, but only minimally impacts the frequency of long term repopulating HSCs (LT-HSCs). It has been variously reported that Runx1 loss increases LT-HSC numbers, decreases LT-HSC numbers, or causes age-related HSC exhaustion. We attempt to resolve these discrepancies by showing that Runx1 deficiency alters the expression of several key HSC markers, and that the number of functional LT-HSCs varies depending on the criteria used to score them. Finally, we identify genes and pathways, including the cell cycle and p53 pathways that are dysregulated in Runx1 deficient HSCs

ESR dosimetry study for the residents of Kazakhstan exposed to radioactive fallout on 24, August 1956

Abstract The method of electron spin resonance (ESR) dosimetry has been applied to human tooth enamel in order to obtain individual absorbed doses from the population of settlements within the vicinity of the central axis of the radioactive fallout trace from the contaminating nuclear surface test of 24, August 1956. Most of the settlements (Glubokoe, Tavriya, and Gagarino) are located near Ust-Kamenogorsk city, in Kazakhstan (about 400 km to the east from the epicenter of the explosion at the Semipalatinsk Nuclear Test Site (SNTS)). It was found that the excess doses obtained after the subtraction of natural background radiation ranged up to about 120 mGy for the residents of Ust-Kamenogorsk city, whose tooth enamel was formed before 1956. For the residents of Gagarino, excess doses do not exceed 47 mGy for all ages. For the residents of Tavriya, the maximum of excess dose was determined as 54 mGy and for the residents of Glubokoe, the maximum excess dose was about 83 mGy. For the population of the Shemonaikha settlements (about 70 km from the centerline of the radioactive fallout trace) the highest excess dose is 110 mGy. Also for this study, Znamenka village (about 130 km from the epicenter) was included. The Kokpekty settlement was chosen as a control and not subjected to any radioactive contamination and is located 400 km to the Southeast from SNTS