Acute Myeloid Leukemia (AML) with rearranged PICALM::MLLT10 is a rare and poorly characterized entity. Here, we describe a patient with this rearrangement, and compare this case to the literature. We Show more
Acute Myeloid Leukemia (AML) with rearranged PICALM::MLLT10 is a rare and poorly characterized entity. Here, we describe a patient with this rearrangement, and compare this case to the literature. We observed a trend towards young age, male sex, extramedullary involvement (particularly mediastinal myelosarcoma), trisomy 4, trisomy 19 and aberrant CD7-expression. It was suggested that upregulation of DOT1l or BMI1 is a key effector for subsequent leukemogenesis. However, molecular data are not available for most published cases. Interestingly, two different EZH2-mutations were detected in our case, while generally being rare in AML, which is concordant with recent reports on the occurrence of EZH2mut in this AML subtype. As a synergistic effect of BMI1 and EZH2 has already been demonstrated in other neoplasms, we hypothesize that acquiring an EZH2 mutation might be a crucial proliferation advantage in PICALM::MLLT10 positive cells. This may explain the high percentage of EZH2 mutated cases in this entity, but also supports the hypothesis of BMI1-mediated leukemogenesis. Show less
Growing interest in the sources of origin of blood vessel related diseases has led to an increasing knowledge about the heterogeneity and plasticity of endothelial cells lining arteries and veins. So Show more
Growing interest in the sources of origin of blood vessel related diseases has led to an increasing knowledge about the heterogeneity and plasticity of endothelial cells lining arteries and veins. So far, most of these studies were performed on animal models. Here, we hypothesized that the plasticity of human fetal endothelial cells depends on their vascular bed of origin i.e. vein or artery and further that the differences between arterial and venous endothelial cells would extend to phenotype and genotype. We established a method for the isolation of fetal arterial and venous endothelial cells from the human placenta and studied the characteristics of both cell types. Human placental arterial endothelial cells (HPAEC) and human placental venous endothelial cells (HPVEC) express classical endothelial markers and differ in their phenotypic, genotypic, and functional characteristics: HPAEC are polygonal cells with a smooth surface growing in loose arrangements and forming monolayers with classical endothelial cobblestone morphology. They express artery-related genes (hey-2, connexin 40, depp) and more endothelial-associated genes than HPVEC. Functional testing demonstrated that vascular endothelial growth factors (VEGFs) induce a higher proliferative response on HPAEC, whereas placental growth factors (PlGFs) are only effective on HPVEC. HPVEC are spindle-shaped cells with numerous microvilli at their surface. They grow closely apposed to each other, form fibroblastoid swirling patterns at confluence and have shorter generation and population doubling times than HPAEC. HPVEC overexpress development-associated genes (gremlin, mesenchyme homeobox 2, stem cell protein DSC54) and show an enhanced differentiation potential into adipocytes and osteoblasts in contrast to HPAEC. These data provide collective evidence for a juvenile venous and a more mature arterial phenotype of human fetal endothelial cells. The high plasticity of the fetal venous endothelial cells may reflect their role as tissue-resident endothelial progenitors during embryonic development with a possible benefit for regenerative cell therapy. Show less