SHP-2 and myeloid malignancies

Marco Tartaglia, Charlotte M. Niemeyer, Kevin M. Shannon, Mignon L. Loh

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Purpose of review: This review focuses on the non-receptor Src-homology 2 domain-containing protein tyrosine phosphatase SHP-2 and its role in signal transduction, hematopoiesis, and leukemogenesis. Specifically, we discuss the role of inherited and somatic mutations that result in SHP-2 gain-of-function in human disease, including myeloid malignancies. Recent findings: Up-regulation of RAS signaling is a major perturbation that drives the aberrant growth of malignant myeloid cells. Leukemia-associated SHP-2 mutations define a novel type of molecular events resulting in hyperactive RAS function. Summary: SHP-2 plays an important role in intracellular signaling elicited by growth factors, hormones, and cytokines, and it is required during development and hematopoiesis. Gain of function mutations in PTPN11, the gene encoding SHP-2, is observed in Noonan syndrome and related development disorders, as well as in myeloid malignancies. Fully characterizing the incidence and spectrum of PTPN11 mutations in hematologic malignancies, and in other forms of cancer, is an area of active investigation.

Original languageEnglish
Pages (from-to)44-50
Number of pages7
JournalCurrent Opinion in Hematology
Volume11
Issue number1
DOIs
Publication statusPublished - Jan 2004

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Mutation
Hematopoiesis
Neoplasms
SH2 Domain-Containing Protein Tyrosine Phosphatases
Noonan Syndrome
Protein Tyrosine Phosphatases
Hematologic Neoplasms
Myeloid Cells
Growth Hormone
Signal Transduction
Intercellular Signaling Peptides and Proteins
Leukemia
Up-Regulation
Cytokines
Incidence
Growth
Genes

Keywords

  • Gain of function
  • JMML
  • Leukemogenesis
  • Noonan syndrome
  • PTPN11
  • RAS signaling

ASJC Scopus subject areas

  • Hematology

Cite this

SHP-2 and myeloid malignancies. / Tartaglia, Marco; Niemeyer, Charlotte M.; Shannon, Kevin M.; Loh, Mignon L.

In: Current Opinion in Hematology, Vol. 11, No. 1, 01.2004, p. 44-50.

Research output: Contribution to journalArticle

Tartaglia, Marco ; Niemeyer, Charlotte M. ; Shannon, Kevin M. ; Loh, Mignon L. / SHP-2 and myeloid malignancies. In: Current Opinion in Hematology. 2004 ; Vol. 11, No. 1. pp. 44-50.
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