Letter to the Editor Leukemia (2010) 24, 232–235; doi:10.1038/leu.2009.200; published online 24 September 2009 PTPN11 mutations in childhood acute lymphoblastic leukemia occur as a secondary event associated with high hyperdiploidy C G Molteni1, G te Kronnie2, S Bicciato3, T Villa1, M Tartaglia4, G Basso2, A Biondi1,5 and G Cazzaniga1,5 1Centro Ricerca Tettamanti, Clinica Pediatrica Università Milano-Bicocca, Ospedale San Gerardo, Monza, Italy 2Laboratorio di Onco-Ematologia, Clinica Pediatrica, Università di Padova, Padua, Italy 3Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, Modena, Italy 4Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanità, Rome, Italy Correspondence: G Cazzaniga, E-mail: gianni.cazzaniga@pediatriamonza.it 5AB and GC share the seniorship of this paper. The protein tyrosine phosphatase, non-receptor type 11 (PTPN11) gene encodes SHP-2, a phosphatase involved in many signaling pathways, with a key role in development and hematopoiesis. Somatic PTPN11 mutations were found with variable prevalences in pediatric leukemia, most frequently associated with juvenile myelomonocytic leukemia (JMML).1, 2 In vitro and in vivo studies, mainly in a myeloid context, demonstrated a crucial involvement of PTPN11 mutations in the hyperactivation of the RAS/ERK pathway.3 The oligoclonality of transgene integration sites, and the long latency before overt leukemia in mice transduced with mutant PTPN11,3 suggested that additional molecular lesions are needed to cooperate with PTPN11 mutations in leukemogenesis. This observation is in line with the ‘two hit model’ proposed by Greaves4 for B-cell precursor childhood acute lymphoblastic leukemia (ALL), in which an initiating alteration, often occurring prenatally, gives rise to a preleukemic clone, which eventually becomes fully malignant by subsequent acquisition of other molecular alterations.
PTPN11 mutations in childhood acute lymphoblastic leukemia occur as a secondary event associated with high hyperdiploidy
TE KRONNIE, GEERTRUDY;BASSO, GIUSEPPE;
2010
Abstract
Letter to the Editor Leukemia (2010) 24, 232–235; doi:10.1038/leu.2009.200; published online 24 September 2009 PTPN11 mutations in childhood acute lymphoblastic leukemia occur as a secondary event associated with high hyperdiploidy C G Molteni1, G te Kronnie2, S Bicciato3, T Villa1, M Tartaglia4, G Basso2, A Biondi1,5 and G Cazzaniga1,5 1Centro Ricerca Tettamanti, Clinica Pediatrica Università Milano-Bicocca, Ospedale San Gerardo, Monza, Italy 2Laboratorio di Onco-Ematologia, Clinica Pediatrica, Università di Padova, Padua, Italy 3Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, Modena, Italy 4Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanità, Rome, Italy Correspondence: G Cazzaniga, E-mail: gianni.cazzaniga@pediatriamonza.it 5AB and GC share the seniorship of this paper. The protein tyrosine phosphatase, non-receptor type 11 (PTPN11) gene encodes SHP-2, a phosphatase involved in many signaling pathways, with a key role in development and hematopoiesis. Somatic PTPN11 mutations were found with variable prevalences in pediatric leukemia, most frequently associated with juvenile myelomonocytic leukemia (JMML).1, 2 In vitro and in vivo studies, mainly in a myeloid context, demonstrated a crucial involvement of PTPN11 mutations in the hyperactivation of the RAS/ERK pathway.3 The oligoclonality of transgene integration sites, and the long latency before overt leukemia in mice transduced with mutant PTPN11,3 suggested that additional molecular lesions are needed to cooperate with PTPN11 mutations in leukemogenesis. This observation is in line with the ‘two hit model’ proposed by Greaves4 for B-cell precursor childhood acute lymphoblastic leukemia (ALL), in which an initiating alteration, often occurring prenatally, gives rise to a preleukemic clone, which eventually becomes fully malignant by subsequent acquisition of other molecular alterations.
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
