ALK-positive Large B-cell Lymphomas with Cryptic SEC31A-ALK and NPM1-ALK Fusions

Overview

Journal Haematologica

Specialty Hematology

Date 2010 Mar 9

PMID 20207848

Citations 33

Authors

Katrien Van Roosbroeck

Jan Cools

Daan Dierickx

Jose Thomas

Peter Vandenberghe

Michel Stul

Jan Delabie

Chris de Wolf-Peeters

Peter Marynen

Iwona Wlodarska

Affiliations

Soon will be listed here.

Abstract

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.

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