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MicroRNA-125b (miR-125b) is up-regulated in patients with leukemia. Overexpression of miR-125b alone in mice causes a very aggressive, transplantable myeloid leukemia. Before leukemia, these mice do not display elevation of white blood cells in the spleen or bone marrow; rather, the hematopoietic compartment shows lineage-skewing, with myeloid cell numbers dramatically increased and B-cell numbers severely diminished. miR-125b exerts this effect by up-regulating the number of common myeloid progenitors while inhibiting development of pre-B cells. We applied a miR-125b sponge loss of function system in vivo to show that miR-125b physiologically regulates hematopoietic development. Investigating the mechanism by which miR-125b regulates hematopoiesis, we found that, among a panel of candidate targets, the mRNA for Lin28A, an induced pluripotent stem cell gene, was most repressed by miR-125b in mouse hematopoietic stem and progenitor cells. Overexpressing Lin28A in the mouse hematopoietic system mimicked the phenotype observed on inhibiting miR-125b function, leading to a decrease in hematopoietic output. Relevant to the miR-125b overexpression phenotype, we also found that knockdown of Lin28A led to hematopoietic lineage-skewing, with increased myeloid and decreased B-cell numbers. Thus, the miR-125b target Lin28A is an important regulator of hematopoiesis and a primary target of miR-125b in the hematopoietic system.

Abstract Pancreaticoduodenectomy (PD) in patients with severe mesenteric atherosclerosis carries a risk of hepatic and intestinal ischemia after ligation of the gastroduodenal artery (GDA). We report the case of a 69-year-old male with pancreatic head adenocarcinoma who underwent PD. Intraoperatively, hepatic artery flow was only pressure-dependent after GDA division. Postoperatively, he developed abdominal pain and emesis. Computerized tomography angiogram showed near-occlusive celiac and thrombosed superior mesenteric artery (SMA) with inferior mesenteric artery (IMA) collateralization. SMA stenting via the left brachial artery restored flow and resolved symptoms. This case underscores the importance of assessing mesenteric perfusion and considering early SMA stenting in high-risk patients prior to PD.