CURRENT PUBLICATIONS (Ranked by Impact Factor of the Journal) LABORATORY RESEARCH KLF1 Regulates BCL11A Expression and Gamma- to Beta-Globin Gene Switching Researchers show that knockdown of KLF1 in human and mouse adult erythroid progenitors markedly reduces BCL11A levels and increases human gamma-globin/beta-globin expression ratios. [Nat Genet] Germline CBL Mutations Cause Developmental Abnormalities and Predispose to Juvenile Myelomonocytic Leukemia Researchers describe a dominant developmental disorder resulting from germline missense CBL mutations, which is characterized by impaired growth, developmental delay, cryptorchidism and a predisposition to juvenile myelomonocytic leukemia. [Nat Genet] Haploinsufficiency for the Erythroid Transcription Factor KLF1 Causes Hereditary Persistence of Fetal Hemoglobin Functional assays suggested that, in addition to its established role in regulating adult globin expression, KLF1 is a key activator of the BCL11A gene, which encodes a suppressor of fetal hemoglobin (HbF) expression. These observations provide a rationale for the effects of KLF1 haploinsufficiency on HbF levels. [Nat Genet] Aryl Hydrocarbon Receptor Antagonists Promote the Expansion of Human Hematopoietic Stem Cells Although practiced clinically for over 40 years, the use of hematopoietic stem cell (HSC) transplants remains limited by the ability to expand these cells ex vivo. An unbiased screen with primary human HSC identified a purine derivative, StemRegenin 1, that promotes the ex vivo expansion of CD34+ cells. [Science] CCR7 Impairs Hematopoiesis Following Hematopoietic Stem Cell Transplantation Increasing Susceptibility to Invasive Aspergillosis Researchers investigated the role of CCR7 in a murine model of invasive aspergillosis following combined hematopoietic stem cell and myeloid progenitor cell transplantation into lethally irradiated wild-type mice. [Blood] Genetic Manipulation of AML1-ETO-Induced Expansion of Hematopoietic Precursors in a Drosophila Model Among mutations in human Runx1/AML1 transcription factors, the t(8;21)(q22;q22) genomic translocation that creates an AML1-ETO fusion protein is implicated in etiology of the acute myeloid leukemia. To identify genes and components associated with this oncogene researchers employed Drosophila as a genetic model. [Blood] c-Myb Supports Erythropoiesis Through the Transactivation of KLF1 and LMO2 Expression The c-Myb transcription factor is highly expressed in immature hematopoietic cells and down-regulated during differentiation. To define its role during the hematopoietic lineage commitment, researchers silenced c-Myb in human CD34+ hematopoietic stem/progenitor cells. [Blood] Polarization and Migration of Hematopoietic Stem and Progenitor Cells Rely on RhoA/ROCK I Pathway and an Active Reorganization of the Microtubule Network Here, researchers investigated the role of the Rho kinase pathway in the morphology and migration of hematopoietic progenitors using an ex vivo co-culture consisting of human primary CD34+ progenitors and mesenchymal stromal cells. [J Biol Chem] CLINICAL RESEARCH Randomized Study of Induction Therapy Comparing Standard-Dose Idarubicin with High-Dose Daunorubicin in Adult Patients with Previously Untreated Acute Myeloid Leukemia Researchers conducted a multi-institutional randomized study to determine whether high-dose daunorubicin would be as effective as standard-dose idarubicin in remission induction therapy for newly diagnosed adult patients aged younger than 65 with acute myeloid leukemia. [Blood] Allogeneic Hematopoietic Cell Transplantation for Hematological Malignancy: Relative Risks and Benefits of Double Umbilical Cord Blood Researchers studied 536 patients at the Fred Hutchinson Cancer Research Center and University of Minnesota with malignant disease who underwent transplant with an HLA matched related donor (MRD, n=204), HLA allele matched or 1-antigen mismatched unrelated adult donor (MUD, n=152; MMUD, n=52) or 4-6/6 HLA matched double umbilical cord blood (n=128) graft after myeloablative conditioning. [Blood] Hematopoietic Stem Cell Transplantation for Therapy-Related Myelodysplastic Syndrome and Acute Leukemia: a Single-Center Analysis of 47 Patients Although this study has several limitations, including a potential selection bias due to the retrospective nature of the analysis and a small number of patients, the results show that modern hematopoietic stem cell transplantation may be useful for inducing long-term survival in a fraction of patients suffering from therapy-related myelodysplastic syndrome and acute leukemia. The present findings warrant future prospective studies. [Int J Hematol]
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