Abruzzo, Lynne V., Herling, Carmen D., Calin, George A., Oakes, Christopher, Barron, Lynn L., Banks, Haley E., Katju, Vikram, Keating, Michael J. and Coombes, Kevin R. (2018). Trisomy 12 chronic lymphocytic leukemia expresses a unique set of activated and targetable pathways. Haematologica, 103 (12). S. 2069 - 2079. PAVIA: FERRATA STORTI FOUNDATION. ISSN 0390-6078

Full text not available from this repository.

Abstract

Although trisomy 12 (+12) chronic lymphocytic leukemia (CLL) comprises about 20% of cases, relatively little is known about its pathophysiology. These cases often demonstrate atypical morphological and immunophenotypic features, high proliferative rates, unmutated immunoglobulin heavy chain variable region genes, and a high frequency of NOTCH1 mutation. Patients with +12 CLL have an intermediate prognosis, and show higher incidences of thrombocytopenia, Richter transformation, and other secondary cancers. Despite these important differences, relatively few transcriptional profiling studies have focused on identifying dysregulated pathways that characterize +12 CLL, and most have used a hierarchical cytogenetic classification in which cases with more than one recurrent abnormality are categorized according to the abnormality with the poorest prognosis. In this study, we sought to identify protein-coding genes whose expression contributes to the unique pathophysiology of +12 CLL. To exclude the likely confounding effects of multiple cytogenetic abnormalities on gene expression, our +12 patient cohort had +12 as the sole abnormality. We profiled samples obtained from 147 treatment-naive patients. We compared cases with +12 as the only cytogenetic abnormality to cases with only del(13q), del(11q), or diploid cytogenetics using independent discovery (n=97) and validation (n=50) sets. We demonstrate that CLL cases with +12 as the sole abnormality express a unique set of activated pathways compared to other cytogenetic subtypes. Among these pathways, we identify the NFAT signaling pathway and the immune checkpoint molecule, NT5E (CD73), which may represent new therapeutic targets.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Abruzzo, Lynne V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herling, Carmen D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Calin, George A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oakes, ChristopherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barron, Lynn L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Banks, Haley E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Katju, VikramUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Keating, Michael J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coombes, Kevin R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-164925
DOI: 10.3324/haematol.2018.190132
Journal or Publication Title: Haematologica
Volume: 103
Number: 12
Page Range: S. 2069 - 2079
Date: 2018
Publisher: FERRATA STORTI FOUNDATION
Place of Publication: PAVIA
ISSN: 0390-6078
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NF-KAPPA-B; CELLS; GENE; CLL; IBRUTINIB; DISEASE; BTK; MICROENVIRONMENT; INHIBITOR; MUTATIONSMultiple languages
HematologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16492

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item