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Prognostic information and biological insights in chronic lymphocytic leukemia by high‐resolution immunophenotypic analysis of ZAP70
Author(s) -
Kaplan David,
Sun Zhuoxin,
Tallman Martin S.,
Flinn Ian W.,
Xiao Wenbin,
Caimi Paolo F.,
Kaye Nicholas M.,
Lazarus Hillard M.
Publication year - 2014
Publication title -
cytometry part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.316
H-Index - 90
eISSN - 1552-4930
pISSN - 1552-4922
DOI - 10.1002/cyto.a.22485
Subject(s) - zap70 , chronic lymphocytic leukemia , flow cytometry , immunophenotyping , biology , cancer research , computational biology , immunology , leukemia , t cell , t cell receptor , immune system
The E2997 Phase III trial included preservation of valuable chronic lymphocytic leukemia (CLL) patient specimens and relevant clinical outcome data. Using a novel high‐resolution technology on a flow cytometry platform, we assessed 79 E2997 samples for the expression of 27 analytes that reflected the activity of signaling pathways and apoptosis. We found that the expression levels of ZAP70 segregated the samples into two subpopulations with the distribution showing a peak‐trough‐peak configuration. Although prior assessment of ZAP70 by standard procedures did not reveal any prognostic information, we found by using the trough in the distribution as a cutpoint that ZAP70 expression levels were significantly correlated with both progression‐free survival and overall survival. Additionally, the cells expressing high versus low levels of ZAP70 demonstrated distinct molecular organization as indicated by the other analytes assessed. Our analysis demonstrates the value of ZAP70 expression as a prognostic indicator and suggests that the different clinical results may be due to the distinct molecular biology of the ZAP70‐low versus the ZAP70‐high CLL samples. © 2014 International Society for Advancement of Cytometry