Hematopoiesis News Volume 4.25 | Jul 2 2013

A Stable Transcription Factor Complex Nucleated by Oligomeric AML1-ETO Controls Leukemogenesis
Scientists showed that, in human leukemic cells, AML1-ETO resides in and functions through a stable AML1-ETO-containing transcription factor complex (AETFC) that contains several hematopoietic transcription (co)factors. These AETFC components stabilize the complex through multivalent interactions, provide multiple DNA-binding domains for diverse target genes, co-localize genome wide, cooperatively regulate gene expression, and contribute to leukemogenesis. [Nature] Abstract

The Lin28b-let-7-Hmga2 Axis Determines the Higher Self-Renewal Potential of Fetal Hematopoietic Stem Cells
Mouse hematopoietic stem cells (HSCs) undergo a postnatal transition in several properties, including a marked reduction in their self-renewal activity. Researchers now show that the developmentally timed change in this key function of HSCs is associated with their decreased expression of Lin28b and an accompanying increase in their let-7 microRNA levels. [Nat Cell Biol] Abstract

The Satb1 Protein Directs Hematopoietic Stem Cell Differentiation toward Lymphoid Lineages
Researchers searched for key factors that direct hematopoietic stem cells (HSCs) to lymphopoiesis. Comparing gene expression profiles for HSCs and early lymphoid progenitors revealed that Satb1, a global chromatin regulator, was markedly induced with lymphoid lineage specification. [Immunity] Abstract

TXNIP Maintains the Hematopoietic Cell Pool by Switching the Function of p53 under Oxidative Stress
Reactive oxygen species (ROS) are critical determinants of the fate of hematopoietic stem cells (HSCs) and hematopoiesis. Thioredoxin-interacting protein (TXNIP), which is induced by oxidative stress, is a known regulator of intracellular ROS. Txnip-/- old mice exhibited elevated ROS levels in hematopoietic cells and showed a reduction in hematopoietic cell population. [Cell Metab] Abstract | Graphical Abstract

TET1 Plays an Essential Oncogenic Role in MLL-Rearranged Leukemia
In contrast to the frequent down-regulation (or loss-of-function mutations) and critical tumor-suppressor roles of the three ten-eleven translocation (TET) genes observed in various types of cancers, here researchers showed that TET1 is a direct target of MLL-fusion proteins and is significantly up-regulated in MLL-rearranged leukemia, leading to a global increase of 5-hydroxymethylcytosine level. [Proc Natl Acad Sci USA] Abstract

Multimodal Imaging Reveals Structural and Functional Heterogeneity in Different Bone Marrow Compartments: Functional Implications on Hematopoietic Stem Cells
Using the combination of whole body optical imaging, intravital microscopy and “in vivo fluorescence trapping”, a thorough comparison of hematopoietic stem cells (HSCs) and putative HSC niches in the calvaria, epiphyses and diaphyses, at steady state or after HSC transplantation, can be made. Researchers report substantial heterogeneity between different bone marrow compartments in terms of bone remodeling activity, blood volume fraction and hypoxia. [Blood] Abstract

Live Cell Detection of Chromosome 2 Deletion and Sfpi1/PU1 Loss in Radiation-Induced Mouse Acute Myeloid Leukemia
Using a genetically engineered C57BL/6 mouse model expressing the GFP fluorescent molecule under the control of the Sfpi1 promoter, which the authors have bred onto the radiation-induced acute myeloid leukemia-susceptible CBA/H strain, they demonstrated that GFP expression did not interfere with X-ray induced leukemia incidence and that GFP fluorescence in live leukemic cells is a surrogate marker of radiation-induced chromosome 2 deletions with or without point mutations on the remaining allele of the Sfpi1 gene. [Leuk Res] Full Article

CLINICAL RESEARCH

Role of Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem-Cell Transplantation in Older Patients with De Novo Myelodysplastic Syndromes: An International Collaborative Decision Analysis
Researchers evaluated reduced-intensity conditioning transplantation versus nontransplantation therapies in older patients with myelodysplastic syndromes stratified by International Prognostic Scoring System risk. [J Clin Oncol] Abstract | Press Release

Unrelated Donor Allogeneic Hematopoietic Cell Transplant Is Under-Utilized as a Curative Therapy in Eligible Patients from the United States
To determine the utilization of allogeneic hematopoietic cell transplant (alloHCT) from unrelated donors (URD) in the United States, the authors calculated the number of cases diagnosed with hematologic disorders aged 20 to 74 years, estimated the percentage of patients who would be eligible for URD alloHCT after discounting the mortality rate during induction therapy and the rate of severe comorbidities, and compared these with the actual alloHCTs facilitated by the National Marrow Donor Program. [Biol Blood Marrow Transplant] Abstract

Visit our reviews page to see a complete list of reviews in the hematopoietic research field.

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Kiadis Pharma Awarded a €3 Million Innovation Credit from the Dutch Government for Phase II Clinical Development Program
Kiadis Pharma B.V. announced that it will receive an innovation credit of up to €3 million from AgentschapNL, a division of the Dutch Ministry of Economic Affairs, to support the Phase II clinical development of Kiadis Pharma’s lead pipeline product, ATIR™. Kiadis Pharma is currently conducting a Phase II international multi-center study with ATIR™, its cell based product for blood cancers, in order to confirm and extend previous Phase I/II results. [Kiadis Pharma B.V.] Press Release  

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)  

Visit our events page to see a complete list of events in the hematopoietic community.

Research Associate (Assistant Professor) – Pediatric Hematology/Oncology (The University of Chicago)

Postdoctoral Research Fellow – Hematology/Pharmacology (Thomas Jefferson University, Cardeza Foundation for Hematologic Research)

Postdoctoral Positions – Stem Cell Biology and Epigenetics (University of Wisconsin-Madison)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

PhD Student Position – Hematopoietic Stem Cells (Katholieke Universiteit Leuven)

Postdoctoral Fellow – Radiobiology and Hematopoietic Stem Cell Biology (Indiana University School of Medicine)

Postdoctoral Researcher – Hematopoietic Stem Cells (Albert Einstein College of Medicine)

Postdoctoral Fellow – Stem Cells and Cancer (Tsinghua University)

Studentship – Novel Mechanisms in Blood Cancers Drug-Resistance (University of East Anglia)

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