Albert Einstein Cancer Center

Selected Achievements: Stem Cells, Differentiation and Cancer

The Steidl laboratory discovered a novel, homeobox transcription factor (H2.0-like homeobox, HLX) that regulates early hematopoiesis and promotes acute myeloid leukemia, a new oncogene overexpressed in the majority of patients with acute myeloid leukemia (AML) that independently correlates with shorter survival .  (Cancer Cell. 22:194-208, 2012 PMID 22897850) 

 

Steidl and Verma reported that a novel small molecule thrombopoietin receptor agonist (eltrombopag): (i) increases normal megakaryopoiesis without stimulating malignant myeloid cell proliferation in vitro or in vivo (murine xenograft model) and (ii) inhibits the proliferation of leukemia cells by reducing intracellular iron and inducing differentiation. (Blood. 120:386-94, 2012 PMID 22627766; Blood. 114:3899-908, 2009 PMID 19710504) 

The Frenette laboratory reported that increased adrenergic activity in the bone marrow microenvironment enhances hematopoietic stem and progenitor cell mobilization and the migration of monocytes/macrophages. (Frenette PS. Blood. 119:3962-5, 2012 PMID 22422821; Frenette PS. Immunity.  37:290-301, 2012 PMID 22863835) 

 

The Zhu laboratory reported that inactivation of the pRb target Skp2 completely prevents spontaneous pituitary tumor development in Rb1(+/-) mice by preventing p27 ubiquitination by SCF(Skp2) ubiquitin ligase via a pRb-Skp2-p27T187p pathway that can be targeted. (Nat. Genet. 42:83-8, 2010 PMID: 19966802) 

 

The Query laboratory identified a novel mechanism of RNA splicing providing insights into substrate selection during spliceosomal branching catalysis and a potential tool for studying mechanisms in mutated splicing proteins in malignancies. (Mol Cell 34:333–343, 2009 PMID: 19450531; Cell 147:1484–1483, 2011. PMID: 22196726) 

 

The Gamble laboratory reported that (i) histone variants like MacroH2A replace canonical histones in nucleosomes to designate regions of chromatin for specific purposes and, (ii) changes in the alternative splicing of macroH2A1 pre-mRNA, which lead to a decrease in macroH2A1.1 expression, occur in a variety of cancers mediating suppression of proliferation, at least in part, through the reduction of poly(ADP-ribose) polymerase 1 (PARP-1) protein levels. (Mol Cell Biol. 31:4244-55, 2011. PMID 21844227) 

 

In an ECOG study (E1900) of 657 patients with de novo acute myelogenous leukemia, Dr. Paietta showed that expression of CD25 (interleukin-2 receptor-α), independent of integrated cytogenetic and mutational data, correlated with poor prognosis improving the ability to identify patients at high risk of relapse. (Blood. 120:2297-30, 2012. PMID: 22855599) 

 

The Stanley laboratory reported that CSF-1R and its ligands, CSF-1 and IL-34, play a critical role in microglial development and neural progenitor cell differentiation. These findings have important repercussions for understanding brain tumor biology and, with the Segall Laboratory, the role of CSF-1R which directly or via microglial regulation impact on tumor progression (Dev Biol. 367:100-13, 2012. PMID 22542597; Mol Med. 18:519-27, 2012. PMID 22294205 ) 

 

The Chiorazzi laboratory developed the first xenograft model to study primary human CLL cells in vivo by co-transferring autologous T lymphocytes into NSG mice. (Blood. 117:5463-72, 2011. PMID 21385850)  

 

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