PTPN11 mutations in pediatric patients with acute myeloid leukemia: results from the Children's Cancer Group.
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.
Loh
M L
ML
Department of Pediatrics, University of California, San Francisco, CA 94143, USA. lohm@itsa.ucsf.edu <lohm@itsa.ucsf.edu>
Reynolds
M G
MG
Vattikuti
S
S
Gerbing
R B
RB
Alonzo
T A
TA
Carlson
E
E
Cheng
J W
JW
Lee
C M
CM
Lange
B J
BJ
Meshinchi
S
S
D000208:Acute Disease; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins; D007951:Leukemia, Myeloid / Q000145:classification / Q000235:genetics*; D007958:Leukocyte Count; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D018909:src Homology Domains
D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases