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Blood, 15 July 2004, Vol. 104, No. 2, pp. 307-313.
Prepublished online as a Blood First Edition Paper on February 24, 2004; DOI 10.1182/blood-2003-11-3876.
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PLENARY PAPERS
Genetic evidence for lineage-related and differentiation stage–related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia
Marco Tartaglia,
Simone Martinelli,
Giovanni Cazzaniga,
Viviana Cordeddu,
Ivano Iavarone,
Monica Spinelli,
Chiara Palmi,
Claudio Carta,
Andrea Pession,
Maurizio Aricò,
Giuseppe Masera,
Giuseppe Basso,
Mariella Sorcini,
Bruce D. Gelb, and
Andrea Biondi
From the Dipartimento di Biologia cellulare e Neuroscienze and Dipartimento Ambiente e connessa prevenzione primaria, Istituto Superiore di Sanità, Rome, Italy; Centro Ricerca M. Tettamanti, Clinica Pediatrica Università di Milano Bicocca, Monza, Italy; Dipartimento di Pediatria, Università di Padova, Padova, Italy; Dipartimento di Pediatria, Università di Bologna, Bologna, Italy; U.O. Onco-Ematologia Pediatrica, Ospedale dei Bambini "G. Di Cristina," Palermo, Italy; and Departments of Pediatrics and Human Genetics, Mount Sinai School of Medicine, New York, NY.
SHP-2 is a protein tyrosine phosphatase functioning as signal transducer downstream to growth factor and cytokine receptors. SHP-2 is required during development, and germline mutations in PTPN11, the gene encoding SHP-2, cause Noonan syndrome. SHP-2 plays a crucial role in hematopoietic cell development. We recently demonstrated that somatic PTPN11 mutations are the most frequent lesion in juvenile myelomonocytic leukemia and are observed in a smaller percentage of children with other myeloid malignancies. Here, we report that PTPN11 lesions occur in childhood acute lymphoblastic leukemia (ALL). Mutations were observed in 23 of 317 B-cell precursor ALL cases, but not among 44 children with T-lineage ALL. In the former, lesions prevalently occurred in TEL-AML1- cases with CD19+/CD10+/cyIgM- immunophenotype. PTPN11, NRAS, and KRAS2 mutations were largely mutually exclusive and accounted for one third of common ALL cases. We also show that, among 69 children with acute myeloid leukemia, PTPN11 mutations occurred in 4 of 12 cases with acute monocytic leukemia (FAB-M5). Leukemia-associated PTPN11 mutations were missense and were predicted to result in SHP-2 gain-of-function. Our findings provide evidence for a wider role of PTPN11 lesions in leukemogenesis, but also suggest a lineage-related and differentiation stage-related contribution of these lesions to clonal expansion. (Blood. 2004;104:307-313)
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|
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|
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|
|
|
|
|
|
|
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|
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|
|
|
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|
|
|
|
|
|
|
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[Full Text]
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|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
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|
|
|
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|
|
|
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|
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|
|
|
|
|
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|
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|
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