Document Detail


ALK-positive large B-cell lymphomas with cryptic SEC31A-ALK and NPM1-ALK fusions.
MedLine Citation:
PMID:  20207848     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We report 2 ALK-positive large B-cell lymphoma cases showing granular cytoplasmic and cytoplasmic/nuclear ALK immunostaining in which cryptic ALK rearrangements were identified by fluorescent in situ hybridization and molecular analysis. In the first case, the ALK-involving t(2;3)(p23;q27) masked the cryptic SEC31A-ALK fusion generated by an insertion of the 5' end of SEC31A (4q21) upstream of the 3' end of ALK. This rearrangement was associated with loss of the 5' end of ALK and duplication of SEC31A-ALK on der(20). In the second case with complex rearrangements of both chromosomes 2, a submicroscopic NPM1-ALK fusion created by insertion of the 3' end of ALK into the NPM1 locus was evidenced. Further studies of SEC31A-ALK showed that this variant fusion transforms IL3-dependent Ba/F3 cells to growth factor independence, and that the ALK inhibitor TAE-684 reduces cell proliferation and kinase activity of SEC31A-ALK and its downstream effectors ERK1/2, AKT, STAT3 and STAT5.
Authors:
Katrien Van Roosbroeck; Jan Cools; Daan Dierickx; José Thomas; Peter Vandenberghe; Michel Stul; Jan Delabie; Chris De Wolf-Peeters; Peter Marynen; Iwona Wlodarska
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Haematologica     Volume:  95     ISSN:  1592-8721     ISO Abbreviation:  Haematologica     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-08     Completed Date:  2010-07-08     Revised Date:  2011-06-08    
Medline Journal Info:
Nlm Unique ID:  0417435     Medline TA:  Haematologica     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  509-13     Citation Subset:  IM    
Affiliation:
Center for Human Genetics, K.U. Leuven, Gasthuisberg, Herestraat 49, Box 602, B-3000 Leuven, Belgium.
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MeSH Terms
Descriptor/Qualifier:
Adult
Chromosomes, Human / genetics
Female
Gene Rearrangement*
Humans
Immunoenzyme Techniques
In Situ Hybridization, Fluorescence
Karyotyping
Lymphoma, Large B-Cell, Diffuse / genetics*,  metabolism,  pathology
Male
Oncogene Proteins, Fusion / genetics*,  metabolism
Protein-Tyrosine Kinases / genetics*,  metabolism
Vesicular Transport Proteins / genetics*,  metabolism
Chemical
Reg. No./Substance:
0/Oncogene Proteins, Fusion; 0/SEC31A protein, human; 0/Vesicular Transport Proteins; EC 2.7.1.-/p80(NPM-ALK) protein; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.1/anaplastic lymphoma kinase
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