LABORATORY RESEARCH Somatic Mutations Found in the Healthy Blood Compartment of a 115-Year-Old Woman Demonstrate Oligoclonal Hematopoiesis Investigators estimate that approximately 450 somatic mutations accumulated in the nonrepetitive genome within the healthy blood compartment of a 115-year-old woman. The distribution of variant allele frequencies of these mutations suggests that the majority of the peripheral white blood cells were offspring of two related hematopoietic stem cell clones. [Genome Res] Abstract | Full Article | Press Release Key Regulators Control Distinct Transcriptional Programs in Blood Progenitor and Mast Cells Through comparative analysis of 10 key hematopoietic transcription factors in both mast cells and blood progenitors, scientists demonstrate that the largely cell type-specific binding profiles are not opportunistic, but instead contribute to cell type-specific transcriptional control, because mathematical modeling of differential binding of shared transcription factors can explain differential gene expression, consensus binding sites are important for cell type-specific binding and knock-down of blood stem cell regulators in mast cells reveals mast cell-specific genes as direct targets. [EMBO J] Full Article Runx1 Exon 6 Related Alternative Splicing Isoforms Differentially Regulate Hematopoiesis in Mice Investigators characterized three Runx1 isoforms generated by exon 6 alternative splicing. Runx1bEx6- (Runx1b without exon 6) and a unique mouse Runx1bEx6e showed higher colony-forming activity than the full length Runx1b. [Blood] Abstract Identification of the Core Autophagy Protein ATG4B as a Potential Biomarker and Therapeutic Target in CML Stem/Progenitor Cells Researchers demonstrate that several key autophagy genes are differentially expressed in CD34+ hematopoietic stem/progenitor cells, with the highest transcript levels detected for ATG4B, and that the transcript and protein expression levels of ATG4 family members, ATG5 and BECLIN-1, are significantly increased in CD34+ cells from chronic phase chronic myeloid leukemia (CML) patients. [Blood] Abstract Sin3a Associated Hdac1 and Hdac2 Are Essential for Hematopoietic Stem Cell Homeostasis and Contribute Differentially to Hematopoiesis Scientists showed that Hdac1 and Hdac2 collectively control hematopoietic stem cell homeostasis, in a cell-autonomous fashion. Simultaneous loss of Hdac1 and Hdac2 resulted in loss of hematopoietic stem cells and consequently bone marrow failure. [Haematologica] Abstract | Full Article Critical Role for NAD Glycohydrolase in Regulation of Erythropoiesis by Hematopoietic Stem Cells through Control of Intracellular NAD Content Researchers report the structural and functional characterization of a novel NAD glycohydrolase (NADase) from rabbit reticulocytes. The novel NADase is a glycosylated, GPI-anchored cell surface protein, exclusively expressed in reticulocytes. [J Biol Chem] Abstract | Full Article Lineage-Dependent Skewing of Loss of Heterozygosity (LOH) of KRAS Gene in a Case of Juvenile Myelomonocytic Leukemia Researchers present a case of juvenile myelomonocytic leukemia with a KRAS G13D mutation. The mutation was detected in various hematopoietic lineages, including T and B lymphocytes and also in lineage- CD34+CD38– hematopoietic stem cells, showing a different percentage of affected cells in each lineage. [Eur J Haematol] Abstract CLINICAL RESEARCH Phase II Clinical Study of Erlotinib for Treatment of Myelodysplastic Syndromes Outcome in patients with myelodysplastic syndrome (MDS) after azanucleosides failure is poor with unmet need for active novel agents. Preclinical data have suggested that erlotinib has in vivo and in vitro off EGFR-target activity in MDS. Researchers conducted a Phase II study with single-agent erlotinib 150 mg/day orally in MDS patients following azanucleoside failure. [Am J Hematol] Abstract Rescue Stem Cell Mobilization with Plerixafor Economizes Leukapheresis in Patients with Multiple Myeloma Investigators retrospectively assessed the effect of an early plerixafor rescue regimen for mobilization in patients with multiple myeloma. Patients were intended for high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation and therefore received cyclophosphamide-based mobilization chemotherapy and consecutive stimulation with granulocyte colony-stimulating factor. [J Clin Apher] Abstract |