title: Treating leukemia at the risk of inducing severe anemia.
abstract: Anemia is a frequently observed adverse effect in cancer patients who receive chemotherapy or drugs designed to block specific oncogenic signaling pathways, although the underlying mechanisms are poorly understood. An article first published online (Zhu HH, Luo X, Zhang K, et al. Proc Natl Acad Sci USA 2015;112:13342-13347) presented data indicating that cell type-specific pathway cross-talk is likely an important mechanism to consider. Shp2 and Pten, two master regulators of central cytoplasmic signaling pathways, oppose each other in myeloproliferation and leukemogenesis, but cooperate in promoting erythropoiesis. Thus, genetic ablation or pharmacologic inhibition of Shp2 suppresses the leukemogenic effect of Pten loss, yet simultaneously induces severe anemia in mice with Pten deficiency in blood cells.
authors.affiliation: Division of Biological Sciences and Department of Pathology, Moores UCSD Cancer Center, University of California San Diego, La Jolla, CA.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Helen He
authors.initials: HH
authors.lastname: Zhu
authors.affiliation: Division of Biological Sciences and Department of Pathology, Moores UCSD Cancer Center, University of California San Diego, La Jolla, CA. Electronic address: gfeng@ucsd.edu.
authors.forename: Gen-Sheng
authors.initials: GS
authors.lastname: Feng
mesh_terms: D000740:Anemia / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000633:toxicity; D004920:Erythropoiesis / Q000187:drug effects / Q000235:genetics*; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011728:Pyridones / Q000494:pharmacology / Q000633:toxicity; D011744:Pyrimidinones / Q000494:pharmacology / Q000633:toxicity; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*
chemical_list: D004791:Enzyme Inhibitors; D011728:Pyridones; D011744:Pyrimidinones; C560077:trametinib; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; C516725:Ptpn11 protein, mouse; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
references.citation: Nat Rev Mol Cell Biol. 2012 Apr 04;13(5):283-96
references.pmid: 22473468
references.citation: Blood. 2007 Feb 1;109(3):862-7
references.pmid: 17053061
references.citation: Nat Genet. 2003 Jun;34(2):148-50
references.pmid: 12717436
references.citation: Proc Natl Acad Sci U S A. 2015 Oct 27;112(43):13342-7
references.pmid: 26460004
references.citation: Blood. 2004 Mar 15;103(6):2325-31
references.pmid: 14644997
references.citation: Annu Rev Biochem. 2014;83:641-69
references.pmid: 24905788