Volume 2.04 | Feb 1

Hematopoiesis News 2.04, February 1, 2011.  
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Human Tumors Instigate Granulin-Expressing Hematopoietic Cells that Promote Malignancy by Activating Stromal Fibroblasts in Mice 
Scientists demonstrated that Sca1+cKit hematopoietic bone marrow cells of mouse hosts bearing instigating tumors promote the growth of responding tumors that form with a myofibroblast-rich, desmoplastic stroma. [J Clin Invest]



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Newborn Screening Increases Survival Outcome For Patients with Severe Combined Immunodeficiency
A study demonstrates that babies with severe combined immunodeficiency (SCID) who are diagnosed at birth and receive a hematopoietic stem cell transplant have significantly improved survival. [Press release from the American Society of Hematology discussing online prepublication in Blood]

Antibiotic Offers Potential for Anti-Cancer Activity
An antibiotic known for its immunosuppressive functions could also point the way to the development of new anti-cancer agents, researchers reported. [Press release from the Indiana School of Medicine discussing online prepublication in Chemistry & Biology]


CURRENT PUBLICATIONS (Ranked by Impact Factor of the Journal)


Human Thrombopoietin Knockin Mice Efficiently Support Human Hematopoiesis In Vivo
Homozygous humanization of thrombopoietin (TPO) led to increased levels of human engraftment in the bone marrow of the hosts, and multilineage differentiation of hematopoietic cells was improved, with an increased ratio of myelomonocytic verus lymphoid lineages. Moreover, maintenance of human stem and progenitor cells was improved, as demonstrated by serial transplantation. Therefore, RAG2-/-gammac-/- TPO-humanized mice represent a useful model to study human hematopoiesis in vivo. [Proc Natl Acad Sci USA]

Hoxb4-YFP Reporter Mouse Model: A Novel Tool for Tracking Hematopoietic Stem Cell Development and Studying the Role of Hoxb4 in Hematopoiesis
To evaluate accurately the pattern of Hoxb4 expression and gain a better understanding of the physiological role of Hoxb4 in the hematopoietic system, investigators generated a knock-in Hoxb4-YFP reporter mouse model. [Blood]

High-Avidity Cytotoxic-T-Lymphocytes Specific for a New Preferentially Expressed Antigen of Melanoma (PRAME)-Derived Peptide Can Target Leukemic- and Leukemic-Precursor Cells
Since it is likely that an effective anti-tumor response will require high avidity PRAME-specific cytotoxic T lymphocytes (CTLs), scientists attempted to generate such CTLs by using professional and artificial antigen presenting cells loaded with a peptide-library spanning the entire PRAME protein and consisting of 125 synthetic pentadecapeptides, overlapping by 11 amino acids. [Blood]

E47 Regulates Hematopoietic Stem Cell Proliferation and Energetics but not Myeloid Lineage Restriction
Using quantitative in vivo and in vitro approaches, scientists show that E47 is dispensable for the short-term myeloid differentiation of hematopoietic stem cells but regulates their long-term capabilities. [Blood]

CD200 Expression Suppresses Natural Killer Cell Function and Directly Inhibits Patient Anti-Tumor Response in Acute Myeloid Leukemia
Researchers investigated whether CD200 overexpression on acute myeloid leukemia cells could specifically compromise patient natural killer cell anti-tumor responses. [Leukemia]

The Transcription Factor PLAGL2 Activates Mpl Transcription and Signaling in Hematopoietic Progenitor and Leukemia Cells
Scientists have previously shown that the transcription factor PLAGL2 promotes proliferation and cooperates with the leukemia fusion protein Cbfbeta-SMMHC in acute myeloid leukemia development. Here, they show that PLAGL2 upregulates expression of the thrombopoietin receptor Mpl, using two consensus sites in its proximal promoter. [Leukemia]

SHP2 Is a Target of the Immunosuppressant Tautomycetin
SHP2 phosphatase is a positive transducer of growth factor and cytokine signaling. SHP2 is also a bona fide oncogene; gain-of-function SHP2 mutations leading to increased phosphatase activity cause Noonan syndrome, as well as multiple forms of leukemia and solid tumors. Investigators report that tautomycetin (TTN), an immunosuppressor in organ transplantation, and its engineered analog TTN D-1 are potent SHP2 inhibitors. [Chem Biol]

Deletion of Tristetraprolin Caused Spontaneous Reactive Granulopoiesis by a Non-Cell-Autonomous Mechanism Without Disturbing Long-Term Hematopoietic Stem Cell Quiescence
The study’s findings demonstrate the importance of tristetraprolin in inflammatory homeostasis and highlight the ability of the hematopoietic system to respond to stress without significant numbers of quiescent hematopoietic stem cells entering the cell cycle. [J Immunol]


Neonatal Diagnosis of Severe Combined Immunodeficiency Leads to Significantly Improved Survival Outcome: The Case for Newborn Screening
In this comparative study conducted at the two designated severe combined immunodeficiency (SCID) transplant centers in the United Kingdom, researchers show that SCID babies diagnosed at birth because of a positive family history have a significantly improved outcome in comparison to the first presenting family member. [Blood]

Report of a Phase II Study of Clofarabine and Cytarabine in De Novo and Relapsed and Refractory AML Patients and in Selected Elderly Patients at High Risk for Anthracycline Toxicity
The study’s purpose is to determine the efficacy and safety of clofarabine and cytarabine in adult patients with relapsed or refractory acute myeloid leukemia (AML) and in elderly patients with untreated AML and heart disease. [Oncologist]

In Situ RHAMM Protein Expression in Acute Myeloid Leukemia Blasts Suggests Poor Overall Survival
Investigators immunohistochemically analyzed the expression and prognostic significance of the receptor for hyaluronic acid-mediated motility (RHAMM) on trephine bone marrow biopsies from 71 acute myeloid leukemia cases that had been evaluated for cytogenetics and presence of FLT3-internal tandem duplications and NPM1 mutations. [Ann Hematol]


Arteriocyte Receives FDA Approval to Move Forward with Critical Limb Ischemia Trial
Arteriocyte® announced approval from the Food and Drug Administration (FDA) to initiate a Phase I clinical trial using its Magellan MAR01 technology in the treatment of Critical Limb Ischemia. [Arteriocyte® Press Release]

University of Southampton and Inovio Pharmaceuticals Initiate Phase II Clinical Study to Evaluate Leukemia DNA Vaccine Using Electroporation Delivery Technology
Inovio Pharmaceuticals, Inc. announced the regulatory approval of a Phase II clinical trial (WIN Trial) to treat leukemia utilizing Inovio’s new ELGEN 1000 automated vaccine delivery device. [Inovio Pharmaceuticals, Inc. Press Release]

Antisoma Reports Outcome of AS1413 Phase III Trial
Antisoma plc announces that the ACCEDE Phase III trial of AS1413 (amonafide) in secondary acute myeloid leukemia did not meet its primary endpoint. Development of AS1413 will be discontinued. [Antisoma plc Press Release]

NYU Langone Medical Center Establishes The Rita J. and Stanley H. Kaplan Stem Cell/Bone Marrow Transplant Center
New York University (NYU) Langone Medical Center is pleased to announce the opening of The Rita J. and Stanley H. Kaplan Stem Cell/Bone Marrow Transplant Center, dedicated to providing stem cell transplants and comprehensive in-patient and out-patient care for adult and pediatric patients with hematologic cancers. [New York University Langone Medical Center Press Release]

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