title: Role of SHP2 in hematopoiesis and leukemogenesis.
abstract: OBJECTIVE
  SH2 domain-containing tyrosine phosphatase 2 (SHP2), encoded by PTPN11 plays an important role in regulating signaling from cell surface receptor tyrosine kinases during normal development as well as oncogenesis. Herein we review recently discovered roles of SHP2 in normal and aberrant hematopoiesis along with novel strategies to target it.
  
  
  RESULTS
  Cell autonomous role of SHP2 in normal hematopoiesis and leukemogenesis has long been recognized. The review will discuss the newly discovered role of SHP2 in lineage specific differentiation. Recently, a noncell autonomous role of oncogenic SHP2 has been reported in which activated SHP2 was shown to alter the bone marrow microenvironment resulting in transformation of donor derived normal hematopoietic cells and development of myeloid malignancy. From being considered as an 'undruggable' target, recent development of allosteric inhibitor has made it possible to specifically target SHP2 in receptor tyrosine kinase driven malignancies.
  
  
  CONCLUSIONS
  SHP2 has emerged as an attractive target for therapeutic targeting in hematological malignancies for its cell autonomous and microenvironmental effects. However a better understanding of the role of SHP2 in different hematopoietic lineages and its crosstalk with signaling pathways activated by other genetic lesions is required before the promise is realized in the clinic.
authors.affiliation: aDepartment of Pediatrics, Herman B Wells Center for Pediatric Research bDepartment of Microbiology and Immunology cDepartment of Medical and Molecular Genetics dDepartment of Molecular Biology and Biochemistry, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Pandey
authors.forename: Mallika
authors.initials: M
authors.lastname: Saxena
authors.forename: Reuben
authors.initials: R
authors.lastname: Kapur
mesh_terms: D000818:Animals; D002352:Carrier Proteins; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism*; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D010766:Phosphorylation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002352:Carrier Proteins; D047428:Protein Kinase Inhibitors; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11