Document Detail

Relative value of ZAP-70, CD38, and immunoglobulin mutation status in predicting aggressive disease in chronic lymphocytic leukemia.
MedLine Citation:
PMID:  18577710     Owner:  NLM     Status:  MEDLINE    
Leukemia-cell expression of ZAP-70, CD38, or unmutated immunoglobulin heavy chain variable region genes (U-IGHV) each is associated with aggressive disease in patients with chronic lymphocytic leukemia (CLL). To assess the relative strength of each marker, we defined thresholds for designating a case as positive for CD38 or ZAP-70 in a test cohort of 307 patients and used these data-defined criteria to stratify patients in an independent cohort of 705 patients. Multivariable analysis revealed that ZAP-70 was the strongest risk factor. Knowledge of the IGHV mutation status or CD38 did not improve our ability to predict the time to first treatment except for ZAP-70-negative cases, which could be segregated into 2 groups of intermediate-risk or low-risk disease based on whether they expressed unmutated or mutated IGHV. ZAP-70 maintained its high relative prognostic value for the subset of patients with early-stage, asymptomatic disease, including patients evaluated within 1 year of diagnosis. Although it is premature to recommend therapy based on these risk factors, patients with ZAP-70-positive CLL cells should be monitored closely for disease progression as they have a median time from diagnosis to requiring initial therapy by standard criteria of approximately 3 years.
Laura Z Rassenti; Sonia Jain; Michael J Keating; William G Wierda; Michael R Grever; John C Byrd; Neil E Kay; Jennifer R Brown; John G Gribben; Donna S Neuberg; Feng He; Andrew W Greaves; Kanti R Rai; Thomas J Kipps
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-06-24
Journal Detail:
Title:  Blood     Volume:  112     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-26     Completed Date:  2008-09-30     Revised Date:  2013-05-20    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1923-30     Citation Subset:  AIM; IM    
The Chronic Lymphocytic Leukemia Research Consortium, La Jolla, CA, USA.
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MeSH Terms
Aged, 80 and over
Antigens, CD38 / metabolism*
Cohort Studies
Genes, Immunoglobulin Heavy Chain*
Leukemia, Lymphocytic, Chronic, B-Cell / genetics*,  immunology,  metabolism*
Membrane Glycoproteins / metabolism*
Middle Aged
Risk Factors
Tumor Markers, Biological / genetics,  metabolism
ZAP-70 Protein-Tyrosine Kinase / metabolism*
Grant Support
K23 CA115682/CA/NCI NIH HHS; K23 CA115682-03/CA/NCI NIH HHS; K23 CA115682-04/CA/NCI NIH HHS; P01-CA81534/CA/NCI NIH HHS
Reg. No./Substance:
0/Membrane Glycoproteins; 0/Tumor Markers, Biological; EC Protein-Tyrosine Kinase; EC, CD38; EC protein, human

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