Dynamic variation of CD5 surface expression levels within individual chronic lymphocytic leukemia clones
Author(s)
Type
Journal Article
Abstract
Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of clonally derived mature CD5high B cells; however, the cellular origin of CLL is still unknown. Patients with CLL also harbor variable numbers of CD5low B cells, but the clonal relationship of these cells to the bulk disease is unknown and can have important implications for monitoring, treating, and understanding the biology of CLL. Here, we use B-cell receptors (BCRs) as molecular barcodes to first show by single-cell BCR sequencing that the great majority of CD5low B cells in the blood of CLL patients are clonally related to CD5high CLL B cells. We investigate whether CD5 state switching was likely to occur continuously as a common event or as a rare event in CLL by tracking somatic BCR mutations in bulk CLL B cells and using them to reconstruct the phylogenetic relationships and evolutionary history of the CLL in four patients. Using statistical methods, we show that there is no parsimonious route from a single or low number of CD5low switch events to the CD5high population, but rather, large-scale and/or dynamic switching between these CD5 states is the most likely explanation. The overlapping BCR repertoires between CD5high and CD5low cells from CLL patient peripheral blood reveal that CLL exists in a continuum of CD5 expression. The major proportion of CD5low B cells in patients are leukemic, thus identifying CD5low B cells as an important component of CLL, with implications for CLL pathogenesis, clinical monitoring, and the development of anti-CD5-directed therapies.
Date Issued
2017-02-01
Date Acceptance
2016-09-17
Citation
Experimental Hematology, 2017, 46, pp.31-37.e10
ISSN
0301-472X
Publisher
Elsevier
Start Page
31
End Page
37.e10
Journal / Book Title
Experimental Hematology
Volume
46
Copyright Statement
© 2016 ISEH - International Society for Experimental Hematology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000392900400004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Hematology
Medicine, Research & Experimental
Research & Experimental Medicine
B-CELLS
DOWN-REGULATION
APOPTOSIS
LINKING
RNA
Publication Status
Published
Date Publish Online
2016-09-28