LABORATORY RESEARCH Isolation of Single Human Hematopoietic Stem Cells Capable of Long-Term Multilineage Engraftment By tracking the expression of several adhesion molecules in hematopoietic stem cell (HSC)-enriched subsets, researchers revealed CD49f as a specific HSC marker. [Science] Selective Killing of Mixed Lineage Leukemia Cells by a Potent Small-Molecule DOT1L Inhibitor Results provided compelling support for DOT1L inhibition as a basis for targeted therapeutics against mixed lineage leukemia. [Cancer Cell] MLL-Rearranged Leukemia Is Dependent on Aberrant H3K79 Methylation by DOT1L Investigators identified the mixed lineage leukemia (MLL)-fusion targets in an MLL-AF9 leukemia model, and conducted epigenetic profiling for H3K79me2, H3K4me3, H3K27me3, and H3K36me3 in hematopoietic progenitor and leukemia stem cells. [Cancer Cell] The Histone Methyltransferase Inhibitor DZNep Upregulates TXNIP, Increases Reactive Oxygen Species Production, and Targets Leukemia Cells in AML Study demonstrated that 3-Deazaneplanocin A (DZNep) induces robust apoptosis in acute myeloid leukemia (AML) cell lines, primary cells, and targets CD34+CD38– leukemia stem cell-enriched subpopulations. [Blood] Accumulation of Oxidative DNA Damage Restricts the Self-Renewal Capacity of Human Hematopoietic Stem Cells Scientists demonstrated that the serial transplantation of human hematopoietic stem cells (HSCs) into immunodeficient mice triggers replication stress that induces incremental elevation of intracellular reactive oxygen species levels and the accumulation of persistent DNA damage within the human HSCs. [Blood] Prolonged Self-Renewal Activity Unmasks Telomerase Control of Telomere Homeostasis and Function of Mouse Hematopoietic Stem Cells Investigators examined the impact of hematopoietic stem cell (HSC) self-renewal divisions in-vitro and in-vivo on their subsequent regenerative and continuing ability to sustain blood cell production in the absence of telomerase. [Blood] Efficient Hematopoietic Redifferentiation of Induced Pluripotent Stem Cells Derived from Primitive Murine Bone Marrow Cells Scientists generated iPSCs from primitive and non-adherent differentiated bone marrow cells, and compared their differentiation potential to that of fibroblast-derived iPSCs and ESCs. [Stem Cells Dev] The Non-Steroidal Anti-Inflammatory Drugs Sulindac Sulfide and Diclofenac Induce Apoptosis and Differentiation in Human Acute Myeloid Leukemia Cells through an AP-1 Dependent Pathway In this study, a total number of 42 bone marrow derived CD34+ selected de novo acute myeloid leukemia (AML) patient samples and the AML cell lines THP-1 and HL-60 were treated with the non-steroidal anti-inflammatory drugs sulindac sulfide and diclofenac. [Apoptosis] CLINICAL RESEARCH In Vitro Efficacy of Forodesine and Nelarabine (Ara-G) in Pediatric Leukemia To better understand which pediatric patients might benefit from ara-G therapy, scientists investigated the in-vitro sensitivity to these drugs in 96 diagnostic pediatric leukemia patient samples and the mRNA expression levels of different enzymes involved in nucleoside metabolism. [Blood] Reduced-Intensity Conditioning Therapy with Busulfan, Fludarabine, and Anti-Thymocyte Globulin for HLA-Haploidentical Hematopoietic Cell Transplantation in Acute Leukemia and Myelodysplastic Syndrome Investigators assessed 83 patients (age, 16-70 years), 68 with acute leukemia, including 34 in remission and 34 with refractory disease; and 15 patients with myelodysplastic syndrome, in hematopoietic cell transplantation trials utilizing reduced-intensity conditioning with busulfan, fludarabine, and anti-thymocyte globulin. [Blood] Accurate Targeting of Daily Intravenous Busulfan with 8-Hour Blood Sampling in Hospitalized Adult Hematopoietic Cell Transplant Recipients A retrospective pharmacokinetic analysis was conducted in 87 adults receiving daily intravenous busulfan doses administered at the traditional frequency of every 6 hours (TBU) as part of cyclophosphamide followed by TBU, fludarabine monophosphate followed by TBU, or TBU concurrent with fludarabine conditioning. [Biol Blood Marrow Transplant] |