Abstract:
:Chronic lymphocytic leukemia (CLL) patients exhibit a variable clinical course. To investigate the association between clinicobiologic features and responsiveness of CLL cells to anti-IgM stimulation, we evaluated gene expression changes and modifications in cell-cycle distribution, proliferation, and apoptosis of IgV(H) mutated (M) and unmutated (UM) samples upon BCR cross-linking. Unsupervised analysis highlighted a different response profile to BCR stimulation between UM and M samples. Supervised analysis identified several genes modulated exclusively in the UM cases upon BCR cross-linking. Functional gene groups, including signal transduction, transcription, cell-cycle regulation, and cytoskeleton organization, were up-regulated upon stimulation in UM cases. Cell-cycle and proliferation analyses confirmed that IgM cross-linking induced a significant progression into the G(1) phase and a moderate increase of proliferative activity exclusively in UM patients. Moreover, we observed only a small reduction in the percentage of subG(0/1) cells, without changes in apoptosis, in UM cases; contrariwise, a significant increase of apoptotic levels was observed in stimulated cells from M cases. These results document that a differential genotypic and functional response to BCR ligation between IgV(H) M and UM cases is operational in CLL, indicating that response to antigenic stimulation plays a pivotal role in disease progression.
journal_name
Bloodjournal_title
Bloodauthors
Guarini A,Chiaretti S,Tavolaro S,Maggio R,Peragine N,Citarella F,Ricciardi MR,Santangelo S,Marinelli M,De Propris MS,Messina M,Mauro FR,Del Giudice I,Foà Rdoi
10.1182/blood-2007-12-127688subject
Has Abstractpub_date
2008-08-01 00:00:00pages
782-92issue
3eissn
0006-4971issn
1528-0020pii
blood-2007-12-127688journal_volume
112pub_type
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