LABORATORY RESEARCH Niche-Based Screening Identifies Small-Molecule Inhibitors of Leukemia Stem Cells Scientists screened 14,718 compounds in a leukemia-stroma co-culture system for inhibition of cobblestone formation, a cellular behavior associated with stem-cell function. Among those compounds that inhibited malignant cells but spared hematopoietic stem and progenitor cells was the cholesterol-lowering drug lovastatin. [Nat Chem Biol] Abstract miR-142-3p Regulates the Formation and Differentiation of Hematopoietic Stem Cells in Vertebrates Researchers showed that in zebrafish and mouse, miR-142-3p is specifically expressed in hematopoietic stem cells (HSCs). Knockdown of miR-142a-3p in zebrafish led to a reduced population of HSCs in the aorta-gonad-mesonephros region as well as T-cell defects in the thymus. [Cell Res] Abstract Reprogramming of MLL-AF9 Leukemia Cells into Pluripotent Stem Cells Researchers established an acute myeloid leukemia model by over-expressing the human mixed lineage leukemia AF9 (MLL-AF9) fusion gene in mouse hematopoietic cells that carry Yamanaka factors under the control of doxycycline (Dox). Upon addition of Dox in culture, the transplantable leukemia cells were efficiently converted into induced pluripotent stem cells that could form teratomas and produce chimeras. [Leukemia] Abstract | Full Article Inhibition of Plasminogen Activator Inhibitor Type-1 Activity Enhances Rapid and Sustainable Hematopoietic Regeneration The authors demonstrated that BM stromal cells, especially osteoblasts, produce PAI-1 in response to myeloablation, which negatively regulates the hematopoietic regeneration in the BM microenvironment. Genetic disruption of the PAI-1 gene, or pharmacological inhibition of PAI-1 activity, significantly improved the myeloablation-related mortality and promoted rapid hematopoietic recovery after hematopoietic stem cell transplantation through the induction of hematopoiesis-promoting factors. [Stem Cells] Abstract Hematopoietic Expression of Oncogenic BRAF Promotes Aberrant Growth of Monocyte-Lineage Cells Resistant to PLX4720 Researchers generated a mouse model expressing inducible BRAFV600E in the hematopoietic system, and evaluated the efficacy of pathway-targeted therapeutics against primary hematopoietic cells. [Mol Cancer Res] Abstract Nucleostemin Is Indispensable for the Maintenance and Genetic Stability of Hematopoietic Stem Cells Scientists identified an indispensable role of nucleostemin in mouse hematopoietic stem cells (HSCs). Depletion of nucleostemin using short hairpin RNA strikingly impaired the self-renewal activity of HSCs both in vitro and in vivo. Consistently, nucleostemin depletion triggered apoptosis rather than cell-cycle arrest in HSCs. [Biochem Biophys Res Commun] Abstract CLINICAL RESEARCH The Association of Cytochrome P450 Genetic Polymorphisms with Sulfolane Formation and the Efficacy of a Busulfan-Based Conditioning Regimen in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation The authors explored the association between the cytochrome P450 (CYP)2C9, CYP2C19, CYP2B6 and flavin-containing monooxygenase3 genotypes and sulfolane (a water soluble metabolite of busulfan) plasma levels in children undergoing hematopoietic stem cell transplantation. The relationship between these genotypes and the effectiveness of myeloablative conditioning was also analyzed. [Pharmacogenomics J] Abstract Favorable Impact of Pre-Transplant ATG on Outcomes of Reduced-Intensity Hematopoietic Cell Transplants from Partially Mismatched Unrelated Donors Researchers performed a retrospective analysis of 85 patients who received unrelated donor transplants at their institution for hematologic malignancies following conditioning with fludarabine and melphalan, with or without rabbit antithymocyte globulin (ATG). [Bone Marrow Transplant] Abstract Successful Rescue of Early Graft Failure in Pediatric Patients Using T-Cell-Depleted Haploidentical Hematopoietic SCT Graft failure (GF) is a significant complication after allogeneic hematopoietic stem cell transplantation and is associated with a high mortality rate. The authors performed re-transplantation using haploidentical-related donors to rescue children with early GF. [Bone Marrow Transplant] Abstract |