(Washington) – Welcome to “This Week in Blood,” a weekly snapshot of the hottest studies from each week’s issue of Blood, the official journal of the American Society of Hematology (ASH), hand-picked by Blood Editor-in-Chief Bob Löwenberg, MD, and Deputy Editor Nancy Berliner, MD. If you would like a PDF copy of any of the manuscripts highlighted below or would like to request an interview with the author, please email firstname.lastname@example.org.
An epigenetic component of hematopoietic stem cell aging amenable to reprogramming into a young state, Wahlestedt et al.
In this week’s Plenary Paper, Wahlestedt and colleagues use induced pluripotent stem cell (iPSC) technology to analyze the aging defect in hematopoietic stem cells (HSCs). Investigators derived iPSCs from aged hematopoietic progenitors and allowed the cells to reform hematopoiesis in the blastocyst . The functional characteristics of these HSCs turned out to be similar to that of young HSCs, suggesting a reversal of the “aged” phenotype. The rederivation of HSCs that look more like young HSCs confirms that these age-related phenotypic alterations are not a reflection of the accumulation of multiple DNA sequence alterations and mutations. Instead, the authors propose that HSCs undergo an epigenetic “drift” with age that alters the functional characteristics of HSCs but can be reversed with epigenetic reprogramming.
Role of RNA splicing in mediating lineage-specific expression of the von Willebrand factor gene in the endothelium, Yuan et al.
In this week’s issue of Blood, Yuan and colleagues elucidate the role of RNA splicing in tissue-specific expression of von Willebrand factor (vWF) protein. This study confirms that the presence of the first intron of vWF is required for endothelial cell – but not megakaryocyte expression – of vWF. Interestingly, the intron could be replaced by heterologous introns without eliminating expression. Furthermore, the presence of the intron affected protein levels, not RNA levels. These discoveries suggest that the splicing process itself is important for post-transcriptional, tissue-specific expression of vWF. Furthermore, these fascinating insights into the molecular events regulating VWF gene expression may also provide clues to the pathogenesis of von Willebrand disease in patients who have divergent loss of expression between endothelial and platelet vWF.
ARP1 is required for chromosomal translocations, Wray et al.
Because poly ADP ribose polymerase (PARP) inhibitors interfere with DNA repair, many investigators have wondered whether treating patients with them might increase their risk of developing a secondary malignancy, particularly a hematologic malignancy. In this issue of Blood, Wray and colleagues demonstrate with reporter assays that PARP inhibitors actually decrease the rate of chromosomal translocations. The study reveals that PARP is required for the process of alternative non-homologous end joining, one of the DNA repair pathways for double-stranded DNA breaks that can also lead to the generation of chromosomal translocation. In the study, PARP inhibition markedly decreased translocation, suggesting that they may actually be protective against secondary myelodysplastic syndromes and acute myeloid leukemia in the setting of chemotherapy.
Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field of hematology, is available weekly in print and online. Blood is the official journal of the American Society of Hematology (ASH) (www.hematology.org), the world’s largest professional society concerned with the causes and treatment of blood disorders.
ASH’s mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems by promoting research, clinical care, education, training, and advocacy in hematology.
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