1. ¹Department of Pediatrics, University of California, San Francisco, CA, USA
2. ²Comprehensive Cancer Center, University of California, San Francisco, CA, USA
3. ³The Children's Oncology Group, Arcadia, CA, USA
4. ⁴Department of Biostatistics, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA
5. ⁵Program in Human Genetics, University of California, San Francisco, CA, USA
6. ⁶Children's Hospital of Philadelphia, Philadelphia, PA, USA
7. ⁷Department of Pediatrics, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA, USA

Correspondence: Dr ML Loh, Department of Pediatrics, University of California, Room HSE-302, 513 Parnassus Ave., Box 0519, San Francisco, CA 94143, USA. Fax: +1 415 502 5127; E-mail: lohm@itsa.ucsf.edu

Received 28 April 2004; Accepted 23 July 2004; Published online 16 September 2004.

Abstract

The PTPN11 gene encodes SHP-2, a nonreceptor protein tyrosine phosphatase that relays signals from activated growth factor receptors to p21^ras (Ras) and other signaling molecules. Somatic PTPN11 mutations are common in patients with juvenile myelomonocytic leukemia (JMML) and have been reported in some other hematologic malignancies. We analyzed specimens from 278 pediatric patients with acute myelogenous leukemia (AML) who were enrolled on Children's Cancer Group trials 2941 and 2961 for PTPN11 mutations. Missense mutations of PTPN11 were detected in 11 (4%) of these samples. None of these patients had mutations in NRAS; however, one patient had evidence of a FLT3 alteration. Four of the patients with PTPN11 mutations (36%) were boys with French–American–British (FAB) morphology M5 AML (P=0.012). Patients with mutations also presented with elevated white blood cell counts. There was no difference in clinical outcome for patients with and without PTPN11 mutations. These characteristics identify a subset of pediatric AML with PTPN11 mutations that share clinical and biologic features with JMML.