IDENTIFYING THE SUBTYPES OF LEUKEMIA BY CHARACTERIZING THE MUTATIONS OF THE PTPN11 GENE

Intracellular signaling pathways mediate cellular responses to a variety of extracellular signals and dysregulation of such pathways, especially those involved in cell growth and differentiation, is the main cause of cancer. The RAS family of proteins plays key roles in signal transduction, and mutations in RAS proto-oncogenes are involved in about 20% to 30% of all human tumors.

PTPN11 is a cytoplasmic Src homology-2 (SH2) domain-containing protein tyrosine phosphatase that is critical for RAS signaling. Specifically, PTPN11 positively controls RAS function, and is required for the activation of the mitogen-activated protein kinase (MAPK) cascade induced by several growth factors and cytokines.

Professor Bruce Gelb and his team at the Icahn School of Medicine at Mount Sinai discovered that specific mutations of the PTPN11 gene correlate with different types of leukemia.  For example, the mutation Glu76Gly is indicative of juvenile myelomonocyte leukemia (JMML) whereas Glu76Gln is indicative of acute myeloid leukemia (AML).  By characterizing the mutations in PTPN11 in subjects with leukemia, targeted strategies for specific diagnostic, preventive, and therapeutic methods can be developed.

Current Development Status

• Validation in cell models
• Validation using patient samples

Applications

• Personalized medicine for treatment of leukemia

Advantages

• Genetic marker to determine the type of leukemia

Publications

• Tartaglia, M. et al. Nature Genetics, 2003, 34, 148-150

Patent Status

• International Application PCT/US2013/35349 filed November 5, 2003
• Status: Pending
• US Application No. 10/703,210 filed November 5, 2003
• Status: Issued. US Patent No. 7,550,262

Contact

William Chiang, PhD
Business Development Director
Mount Sinai Innovation Partners | Icahn School of Medicine at Mount Sinai
Phone: (609) 575-7033