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PMID: 17519389 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Pathobiology of ALK+ anaplastic large-cell lymphoma.

Blood ·Vol. 110 ·No. 7 ·2007-10-01 ·Pages 2259-67

Amin HM, Lai R

Abstract

Anaplastic large-cell lymphoma (ALCL) was initially recognized on the basis of morphologic features and the consistent expression of CD30. It then became evident that the majority of these tumors are derived from lymphoid cells of T or null immunophenotype. The subsequent finding that t(2;5)(p23;q35) occurs in 40% to 60% of ALCL patients established a distinct clinicopathologic entity. This chromosomal translocation induces the formation of the chimeric protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), which possesses significant oncogenic potential resulting from the constitutive activation of the tyrosine kinase ALK. In addition to its specific pathophysiologic events, NPM-ALK-expressing lymphoma presents with consistent clinical manifestations. Only 13 years after the identification of NPM-ALK, tremendous progress has been made in our understanding of this molecule because of the relentless efforts of multiple investigators who have dissected its biologic roles using in vitro and in vivo experimental models. Several upstream modulators, cross-reacting oncogenes, and downstream effectors of NPM-ALK have been identified and characterized. Understanding these interacting oncogenic systems is expected to facilitate the design of new therapeutic strategies and agents. In this review, we briefly discuss ALCL and focus on NPM-ALK.

MeSH Terms
Anaplastic Lymphoma Kinase Animals Humans Lymphoma, Large-Cell, Anaplastic/enzymology,genetics,pathology,therapy Protein Binding Protein-Tyrosine Kinases/genetics,metabolism Receptor Protein-Tyrosine Kinases Signal Transduction
Chemicals
p80(NPM-ALK) protein ALK protein, human Anaplastic Lymphoma Kinase Protein-Tyrosine Kinases Receptor Protein-Tyrosine Kinases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Amin Hesham M
Department of Hematopathology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA. hamin@mdanderson.org
Lai Raymond
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2007-04-060715
Email
hamin@mdanderson.org
Published
2007-10-01
Epub
2007-00-22
Pages
2259-67
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC1988960
Subset
IM
Grants
NCI NIH HHS · K08 CA114395 · United States
NCI NIH HHS · CA114395 · United States
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PubMed source DOI: 10.1182/blood-2007-04-060715 PMC Full Text View journal details
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