Hematopoiesis News Volume 3.06 | Feb 14 2012

Activation of p53 by SIRT1 Inhibition Enhances Elimination of CML Leukemia Stem Cells in Combination with Imatinib
Researchers show that the NAD⁺-dependent deacetylase SIRT1 is overexpressed in human chronic myelogenous leukemia (CML) stem cells. [Cancer Cell] Abstract | Press Release

N-Cadherin in Osteolineage Cells Is Not Required for Maintenance of Hematopoietic Stem Cells
There is evidence suggesting that N-cadherin expression on osteoblast lineage cells regulates hematopoietic stem cell function and quiescence. To test this hypothesis, scientists conditionally deleted N-cadherin (Cdh2) in osteoblasts using Cdh2^flox/flox Osx-Cre mice. [Blood] Abstract

F Box Protein FBXL2 Targets Cyclin D2 for Ubiquitination and Degradation to Inhibit Leukemic Cell Proliferation
Investigators describe the behavior of a relatively new SCF (Skip-Cullin1-F-box protein) subunit, termed FBXL2, that ubiquitinates and destabilizes cyclin D2 protein leading to G0 phase arrest and apoptosis in leukemic and B lymphoblastoid cell lines. [Blood] Abstract

Knock-In of a FLT3/ITD Mutation Cooperates with a NUP98-HOXD13 Fusion to Generate Acute Myeloid Leukemia in a Mouse Model
Previous work has shown that insertion of a FLT3/ internal tandem duplication (ITD) mutation into the murine Flt3 gene induces a myeloproliferative neoplasm, but not progression to acute leukemia, suggesting that additional cooperating events are required. Scientists combined the FLT3/ITD mutation with a model of myelodysplastic syndrome involving transgenic expression of the Nup98-HoxD13 fusion gene. [Blood] Abstract

Molecular and Cellular Effects of Oncogene Cooperation in a Genetically Accurate AML Mouse Model
Investigators have generated an acute myeloid leukemia (AML) mouse model using knock-in mouse strains to study cooperation of internal tandem duplication mutation in the Flt3 gene with commonly observed C/EBPα mutations. [Leukemia] Abstract

Overexpression of Wild-Type or Mutants Forms of CEBPA Alter Normal Human Hematopoiesis
Data underline the critical role of C/EBPα (CEBPA) in human hematopoiesis and demonstrate that C/EBPα mutations (alone or in combination) are insufficient to convert normal human hematopoietic stem/progenitors into leukemic initiating cells, although individually each altered normal hematopoiesis. [Leukemia] Abstract

Dynamic Interaction Between TAL1 Oncoprotein and LSD1 Regulates TAL1 Function in Hematopoiesis and Leukemogenesis
Here, scientists reported that protein kinase A-mediated phosphorylation regulates TAL1 interaction with the lysine-specific demethylase (LSD1) that removes methyl group from methylated Lys 4 on histone H3 tails. [Oncogene] Abstract

CLINICAL RESEARCH

Early Matched Sibling Hematopoietic-Cell Transplantation for Adult AML in First Remission Using an Age-Adapted Strategy: Long-Term Results of a Prospective GOELAMS Study
The GOELAMS LAM2001 phase III trial, involving 832 patients with acute myeloid leukemia (AML) (median: 46 years, range: 17-60) proposed HLA-identical sibling allograft of hematopoietic stem cells for all patients with an identified donor. [Blood] Abstract

Outcomes After Matched Unrelated Donor vs. Identical Sibling Hematopoietic Cell Transplantation (HCT) in Adults with Acute Myelogenous Leukemia (AML)
Researchers analyzed outcomes of 2,223 adult AML patients who underwent allogeneic HCT between 2002 and 2006 (matched related donor, n=624; 8/8 human leukocyte antigen locus matched unrelated donor (MUD), n=1193; 7/8 MUD, n=406). [Blood] Abstract

FDA Panel Rejects Eisai’s Leukemia Drug
An independent advisory panel to the U.S. health regulator said that Japanese drugmaker Eisai Co Ltd’s Dacogen did not show a favorable risk-benefit profile to treat a type of blood cancer. [U.S. Food and Drug Administration (FDA), United States] Press Release

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