The nucleophosmin-anaplastic lymphoma kinase fusion protein induces c-Myc expression in pediatric anaplastic large cell lymphomas

Elizabeth A. Raetz, Sherrie L. Perkins, Marlee A. Carlson, Kevin Schooler, William L. Carroll, David M. Virshup

Research output: Contribution to journalArticle

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Abstract

The majority of pediatric anaplastic large cell lymphomas (ALCLs) carry the t(2;5)(p23;q35) chromosomal translocation that juxtaposes the dimerization domain of nucleophosmin with anaplastic lymphoma kinase (ALK). The nucleophosmin-ALK fusion induces constitutive, ligand-independent activation of the ALK tyrosine kinase leading to aberrant activation of cellular signaling pathways. To study the early consequences of ectopic ALK activation, a GyrB-ALK fusion was constructed that allowed regulated dimerization with the addition of coumermycin. Expression of the fusion protein caused a coumermycin-dependent increase in cellular tyrosine phosphorylation and c-Myc immunoreactivity, which was paralleled by a rise in c-myc RNA. To assess the clinical relevance of this observation, c-Myc expression was determined in pediatric ALK-positive and -negative lymphomas. Co-expression of c-Myc and ALK was seen in tumor cells in 15 of 15 (100%) ALK-positive ALCL samples, whereas no expression of either ALK or c-Myc was seen in six of six cases of ALK-negative T-cell lymphoma. C-Myc may be a downstream target of ALK signaling and its expression a defining characteristic of ALK-positive ALCLs.

Original languageEnglish (US)
Pages (from-to)875-883
Number of pages9
JournalAmerican Journal of Pathology
Volume161
Issue number3
StatePublished - Sep 2002
Externally publishedYes

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Proto-Oncogene Proteins c-myc
Anaplastic Large-Cell Lymphoma
Pediatrics
Dimerization
nucleophosmin
anaplastic lymphoma kinase
Genetic Translocation
T-Cell Lymphoma
Protein-Tyrosine Kinases
Tyrosine

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Raetz, E. A., Perkins, S. L., Carlson, M. A., Schooler, K., Carroll, W. L., & Virshup, D. M. (2002). The nucleophosmin-anaplastic lymphoma kinase fusion protein induces c-Myc expression in pediatric anaplastic large cell lymphomas. American Journal of Pathology, 161(3), 875-883.

The nucleophosmin-anaplastic lymphoma kinase fusion protein induces c-Myc expression in pediatric anaplastic large cell lymphomas. / Raetz, Elizabeth A.; Perkins, Sherrie L.; Carlson, Marlee A.; Schooler, Kevin; Carroll, William L.; Virshup, David M.

In: American Journal of Pathology, Vol. 161, No. 3, 09.2002, p. 875-883.

Research output: Contribution to journalArticle

Raetz, EA, Perkins, SL, Carlson, MA, Schooler, K, Carroll, WL & Virshup, DM 2002, 'The nucleophosmin-anaplastic lymphoma kinase fusion protein induces c-Myc expression in pediatric anaplastic large cell lymphomas', American Journal of Pathology, vol. 161, no. 3, pp. 875-883.
Raetz, Elizabeth A. ; Perkins, Sherrie L. ; Carlson, Marlee A. ; Schooler, Kevin ; Carroll, William L. ; Virshup, David M. / The nucleophosmin-anaplastic lymphoma kinase fusion protein induces c-Myc expression in pediatric anaplastic large cell lymphomas. In: American Journal of Pathology. 2002 ; Vol. 161, No. 3. pp. 875-883.
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