Hematopoiesis News Volume 3.10 | Mar 13 2012

Inhibition of the LSD1 (KDM1A) Demethylase Reactivates the All-Trans-Retinoic Acid Differentiation Pathway in Acute Myeloid Leukemia
Here scientists show that, through epigenetic reprogramming, inhibitors of lysine-specific demethylase 1 (LSD1, also called KDM1A), including tranylcypromine, unlocked the all-trans-retinoic acid-driven therapeutic response in non-APL AML. [Nat Med] Abstract | Press Release

Leukemia-Initiating Cells of Patient-Derived Acute Lymphoblastic Leukemia Xenografts Are Sensitive Towards TRAIL
Here, researchers investigated whether TRAIL (TNF-related apoptosis-inducing ligand) targets leukemia-initiating cells. [Blood] Abstract

The Pan-Deacetylase Inhibitor Panobinostat Induces Cell Death and Synergizes with Everolimus in Hodgkin Lymphoma Cell Lines
In this study, investigators demonstrate that panobinostat has potent antiproliferative activity against Hodgkin Lymphoma-derived cell lines. [Blood] Abstract

SRC Is a Signaling Mediator in FLT3-ITD But Not in FLT3-TKD Positive AML
Here scientists investigated the mechanisms leading to differential STAT5 activation and show that Fms-like tyrosine kinase 3 (FLT3)-internal tandem duplications (ITD) but not FLT3-tyrosine kinase domain (TKD) utilizes SRC to activate STAT5. [Blood] Abstract

Polycomb Group Ring Finger 1 Cooperates with Runx1 in Regulating Differentiation and Self-Renewal of Hematopoietic Cells
Researchers identify the polycomb group protein Pcgf1 as an epigenetic regulator involved in hematopoietic cell differentiation. They show that simultaneous depletion of Runx1 and Pcgf1 allows sustained self-renewal while blocking differentiation of lineage marker negative cells in vitro. [Blood] Abstract

Early Ontogenic Origin of the Hematopoietic Stem Cell Lineage
To deconvolute hematopoietic ontogeny, investigators designed an embryo-rescue system in which the key hematopoietic factor Runx1 is reactivated in Runx1-null conceptuses at specific developmental stages. [Proc Natl Acad Sci USA] Abstract

Polycomb Repressive Complex 2 Is Required for MLL-AF9 Leukemia
Scientists used conditional alleles for the polycomb repressive complex 2 (PRC2) components enhancer of zeste 2 (Ezh2) and embryonic ectoderm development (Eed) to characterize the role of PRC2 function in leukemia development and progression. [Proc Natl Acad Sci USA] Abstract

Frequent Loss of RAF Kinase Inhibitor Protein Expression in Acute Myeloid Leukemia
Researchers investigated RAF kinase inhibitor protein’s role in acute myeloid leukemia, an aggressive malignancy arising from hematopoietic stem and progenitor cells. [Leukemia] Abstract

5-Aza-2′-Deoxycytidine Induced Growth Inhibition of Leukemia Cells through Modulating Endogenous Cholesterol Biosynthesis
The results from the present study revealed, for the first time, that 5-aza-2′-deoxycytidine exerts its cytotoxic effects in leukemia and melanoma cells through epigenetic reactivation of DPP4 gene and the resultant inhibition of cholesterol biosynthesis in these cells. [Mol Cell Proteomics] Abstract

Induced Transgene Expression for the Treatment of Solid Tumors by Hematopoietic Stem Cell-Based Gene Therapy
Here, researchers describe an alternative approach to treat solid tumors based on the genetic modification of hematopoietic stem and progenitor cells with lentiviral vectors. [Cancer Gene Ther] Abstract

CLINICAL RESEARCH

RIC Is Superior to NMA Conditioning for Older Chronic Myelogenous Leukemia Patients Undergoing Hematopoietic Cell Transplant During the Tyrosine Kinase Inhibitor Era
Investigators analyzed post-hematopoietic cell transplant (HCT) outcomes of 306 CML patients reported to the CIBMTR aged 40 and older undergoing reduced intensity (RIC)/ non-myeloablative (NMA) HCT in 2001-2007: 117 (38%) aged 40-49; 119 (39%) 50-59; and 70 (23%) greater or equal to 60. [Blood] Abstract

Cytogenetic and Molecular Predictors of Response in Patients with Myeloid Malignancies without Del[5q] Treated with Lenalidomide
While lenalidomide (LEN) shows high efficacy in myelodysplastic syndromes with del[5q], responses can be also seen in patients presenting without del[5q]. Scientists hypothesized that improved detection of chromosomal abnormalities with new karyotyping tools may better predict response to LEN. [J Hematol Oncol] Abstract

HemaQuest Pharmaceuticals Raises $13 Million in Series B Extension Financing
HemaQuest Pharmaceuticals, Inc. announced that it has closed a $13 million extension of their Series B financing. Proceeds from the financing will be used to fund a randomized, double-blind, placebo-controlled Phase IIb clinical study evaluating lead product candidate HQK-1001 in patients with sickle cell disease. [HemaQuest Pharmaceuticals, Inc.] Press Release

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

Scientist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

Scientist – hPSC Bioengineering (STEMCELL Technologies Inc.)

Scientist – Antibody and Hybridoma Technology Platforms (STEMCELL Technologies Inc.)

Business Analyst – Product Management (STEMSOFT Software Inc.)

Postdoctoral Fellow in Cytokine Signaling in Hematopoietic Stem Cells (University of Pennsylvania School of Medicine)

Postdoctoral Fellow in Stem Cells and Cancer (Tsinghua University)

Postdoctoral/Research Associate (Children’s Memorial Research Center)


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