Hematopoiesis News Volume 4.23 | Jun 18 2013

LABORATORY RESEARCH

In Vivo RNAi Screening Identifies a Leukemia-Specific Dependence on Integrin Beta 3 Signaling
Scientists used an in vivo small hairpin RNA screening approach to identify genes that are essential for MLL-AF9 acute myeloid leukemia. They found that Integrin Beta 3 is essential for murine leukemia cells in vivo and for human leukemia cells in xenotransplantation studies. [Cancer Cell] Abstract | Graphical Abstract

Targeting Acute Myeloid Leukemia by Dual Inhibition of PI3K Signaling and Cdk9-Mediated Mcl-1 Transcription
The Bcl-2 family member, Mcl-1, is a key driver of cell survival in diverse cancers, including acute myeloid leukemia (AML). A screen for compounds down-regulating Mcl-1 identified the kinase inhibitor, PIK-75, which demonstrates marked pro-apoptotic activity against a panel of cytogenetically diverse primary human AML patient samples. Researchers showed that PIK-75 transiently blocks Cdk7/9, leading to transcriptional suppression of MCL-1, a rapid loss of Mcl-1 protein and alleviation of its inhibition of pro-apoptotic Bak. [Blood] Abstract

Patterns of Missplicing Due to Somatic U2AF1 Mutations in Myeloid Neoplasms
Researchers hypothesized that U2AF1 mutations cause defects of splicing (missplicing) in specific genes and that such misspliced genes might be important in leukemogenesis. [Blood] Abstract

Extramedullary Myelopoiesis in Malaria Depends on Mobilization of Myeloid-Restricted Progenitors by IFN-γ Induced Chemokines
Investigators report the isolation of the earliest myeloid-restricted progenitors in acute infection with the rodent malaria parasite, Plasmodium chabaudi. The rapid disappearance of these infection-induced myeloid progenitors from the bone marrow equated with contraction of the functional myeloid potential in that organ. [PLoS Pathog] Full Article

Chemerin Neutralization Blocks Hematopoietic Stem Cell Osteoclastogenesis
Previously, the authors identified chemerin as a regulator of adipocyte and osteoblast differentiation of mesenchymal stem cells. Herein they examined the role of chemerin in Lin^– Sca1⁺ c-kit⁺ CD34⁺ hematopoietic stem cell osteoclastogenesis. [Stem Cells] Abstract

The Lost Intrinsic Fragmentation of MAT1 Protein during Granulopoiesis Promotes the Growth and Metastasis of Leukemic Myeloblasts
Researchers determined that, in humanized mouse microenvironment, MAT1 overexpression resisted intrinsic MAT1 fragmentation to sustain hematopoietic CD34+ cell expansion while preventing granulopoiesis. [Stem Cells] Abstract

Coordinated Regulation of the Immunoproteasome Subunits by PML/RARα and PU.1 in Acute Promyelocytic Leukemia
It has been established that impairment of the immunoproteasome subunits, that is, PSMB8, PSMB9 and PSMB10 (PSMBs), is critical for malignant cells to escape immune recognition. Researchers report the regulatory mechanism of the repression of PU.1-dependent activation of PSMBs by PML/RARα in the pathogenesis of acute promyelocytic leukemia (APL) and the unidentified function of all-trans retinoic acid as an immunomodulator in the treatment of APL. [Oncogene] Abstract

Overexpression of Jagged-1 and Its Intracellular Domain in Human Mesenchymal Stromal Cells Differentially Affect the Interaction with Hematopoietic Stem and Progenitor Cells
Researchers used genetically engineered bone marrow-derived human mesenchymal stromal cells to study the function role of Jagged-1 and the Jagged-1 intracellular domain with respect to the interaction with hematopoietic stem and progenitor cells. [Stem Cells Dev] Abstract

CLINICAL RESEARCH

A Stem Cell-Like Gene Expression Signature Associates with Inferior Outcomes and a Distinct MicroRNA Expression Profile in Adults with Primary Cytogenetically Normal Acute Myeloid Leukemia
Investigators studied associations of the ‘core enriched’ gene-expression signatures with known molecular prognosticators, microRNA-expression profiles, and outcomes in 364 well-characterized cytogenetically normal-acute myeloid leukemia patients. [Leukemia] Abstract

A Novel Clofarabine Bridge Strategy Facilitates Allogeneic Transplantation in Patients with Relapsed/Refractory Leukemia and High-Risk Myelodysplastic Syndromes
Patients with relapsed/refractory leukemias or advanced myelodysplastic syndrome fare poorly following allogeneic hematopoietic cell transplant (HCT). The authors report prospective phase II study results of 29 patients given clofarabine 30 mg/m²/day i.v. × 5 days followed immediately by HCT conditioning while at the cytopenic nadir. [Bone Marrow Transplant] Abstract

Epigenetics in Clinical Practice: The Examples of Azacitidine and Decitabine in Myelodysplasia (MDS) and Acute Myeloid (AML)
Randomized trials have clearly demonstrated that the hypomethylating agents azacitidine and decitabine are more effective than ‘best supportive care’ (BSC) in reducing transfusion frequency in ‘low risk’ MDS and in prolonging survival compared to BSC or low-dose ara-C in ‘high risk’ MDS or AML with 21-30% blasts. While azacitidine or decitabine are thus the standard to which newer therapies should be compared, here the authors discuss whether the improvement they afford in OS is sufficient to warrant a designation as standard in treating individual patients. [Leukemia] Abstract

The Adolescent and Young Adult with Cancer: State of the Art – Acute Leukemias
Despite survival gains over the past several decades, adolescent and young adult patients with both acute lymphoblastic leukemia and acute myeloid leukemia demonstrate a consistent survival disadvantage. This review highlights distinctive aspects of disease biology in this population, as well as salient treatment-related toxicities including osteonecrosis, pancreatitis, thromboembolism, hyperglycemia, and infections. [Curr Oncol Rep] Abstract

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

Mayo Clinic First in US to Test Stem Cells for Cardiac Regeneration in Pediatric Congenital Heart Patients
Mayo Clinic has announced the first U.S. stem cell clinical trial for pediatric congenital heart disease. The trial aims to determine how stem cells from autologous umbilical cord blood can help children with hypoplastic left heart syndrome, a rare defect in which the left side of the heart is critically underdeveloped. [Mayo Clinic] Press Release

New Sickle Cell Anemia Therapy Advances to Phase II Clinical Trials
The phase II trial, funded by a $10.8 million grant from the National Institutes of Health, is testing an already existing drug called Lexiscan™, which is used for diagnosing heart disease. Researchers are exploring whether the drug’s anti-inflammatory effects will significantly reduce the pain and blood flow disturbances of sickle cell anemia. [La Jolla Institute for Allergy & Immunology] Press Release

Stemline Therapeutics’ SL-401 Receives Orphan Drug Designation for the Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Stemline Therapeutics, Inc. announced that SL-401 has received Orphan Drug designation from the U.S. Food and Drug Administration for the treatment of BPDCN, a rare and aggressive hematologic malignancy for which there is no effective treatment. SL-401 also has Orphan Drug status for the treatment of acute myeloid leukemia. [Stemline Therapeutics, Inc.] Press Release

LifeSouth Reaches a Milestone with FDA License
A journey that began in Gainesville, Florida more than 15 years ago, that’s allowed newborn babies to become lifesavers, reached a milestone, when the Food and Drug Administration (FDA) notified LifeSouth that its license was approved for cord blood manufacturing. [LifeSouth Community Blood Centers]
Press Release

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NEW World Cord Blood Congress 2013
September 30-October 1, 2013
Cambridge, United States

NEW Cell Culture World Congress USA 2013
September 30-October 1, 2013
Cambridge, United States

NEW Stem Cells & Regenerative Medicine Congress 2013
September 30-October 1, 2013
Cambridge, United States

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