LABORATORY RESEARCH CD40 Ligation Reverses T Cell Tolerance in Acute Myeloid Leukemia A murine acute myeloid leukemia (AML) model was used to investigate antigen-specific T cell responses against AML cells inoculated i.v. versus s.c. [J Clin Invest] Full Article Lineage Inappropriate PAX5 Expression in t(8;21) Acute Myeloid Leukemia Requires Signaling Mediated Abrogation of Polycomb Repression To understand the molecular mechanism of PAX5 deregulation, researchers examined its chromatin structure and regulation in t(8;21) acute myeloid leukemia cells, non-t(8;21) myeloid precursor control cells and in pre-B cells. [Blood] Abstract Targeting Oncogene Expression to Endothelial Cells Induces Proliferation of the Myelo-Erythroid Lineage by Repressing the Notch Pathway Investigators used a zebrafish genetic model to induce the expression of oncogenic RAS in endothelial cells, including the hemogenic endothelium of the dorsal aorta that generates hematopoietic cells, and observed the development of a myelo-erythroid proliferative disorder. [Leukemia] Abstract Dynamics of Thymus Organogenesis and Colonization in Early Human Development Researchers demonstrated, via spatial and temporal expression analyses, that the genetic mechanisms known to regulate mouse thymus organogenesis are conserved in humans. They defined the timing of onset of hematopoietic cell colonization and epithelial cell differentiation in the human thymic primordium, showing, unexpectedly, that the first colonizing hematopoietic cells are CD45+CD34int/-. [Development] Full Article Rac1 Signaling Protects Monocytic AML Cells Expressing the MLL-AF9 Oncogene from Caspase-Mediated Apoptotic Death The authors investigated the relevance of signaling mechanisms regulated by the Ras-homologous GTPase Rac1 for survival of acute myeloid leukemia (AML) cells harboring the MLL-AF9 oncogene due to t(9;11)(p21;q23) translocation. [Apoptosis] Abstract Up-Regulated Expression of CXCL12 in Human Spleens with Extramedullary Hematopoiesis Scientists aimed to determine the expression of CXCL12 in human spleens with extramedullary hematopoiesis for clarifying the association of splenic hematopoietic stem cells with CXCL12, which has been demonstrated to be a marker of bone marrow niches. [Pathology] Abstract Self-Renewing Human Bone Marrow Mesenspheres Promote Hematopoietic Stem Cell Expansion Researchers describe a method of isolating and culturing human bone marrow stromal stem/progenitor cells as nonadherent mesenchymal spheres. In culture conditions where they displayed a relatively undifferentiated phenotype, with decreased adherence to plastic and increased self-renewal, they promoted enhanced expansion of cord blood CD34+ cells through secreted soluble factors. Expanded hematopoietic stem cells were serially transplantable in immunodeficient mice and significantly increased long-term human hematopoietic engraftment. [Cell Rep] Abstract | Full Article | Graphical Abstract Effect of Intravenous Coadministration of Human Stroma Cell Lines on Engraftment of Long-Term Repopulating Clonal Myelodysplastic Syndrome Cells in Immunodeficient Mice Investigators used intravenous coadministration of the human marrow stroma cell line HS27a with CD34+ myelodysplastic syndrome (MDS) cells in Nod.cg-Prkdcscid Il2rgtm1wjll mice to provide signals that would facilitate engraftment. Hematopoietic cells from 24 MDS patients were transplanted. [Blood Cancer J] Full Article CLINICAL RESEARCH Early Responses Predicts for Better Outcomes in Patients with Newly Diagnosed CML: Results with Four TKI Modalities Early responses to tyrosine kinase inhibitors (TKI) in CML-CP are associated with improved outcome. The authors analyzed the impact of such response on outcomes among patients treated with 4 TKI modalities as frontline therapy in CML-CP. [Blood] Abstract Old and New Prognostic Factors in Acute Myeloid Leukemia with Deranged Core-Binding Factor Beta Acute myeloid leukemia (AML) with deranged core-binding factor beta (CBFβ) is usually associated with a favorable prognosis with 50-70% of patients cured using contemporary treatments. Researchers analyzed the prognostic significance of clinical features on 58 patients with CBFβ-AML aged ≤60 years. [Am J Hematol] Abstract |