Relative value of ZAP-70, CD38, and immunoglobulin mutation status in predicting aggressive disease in chronic lymphocytic leukemia.

Abstract

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.

• Authors: 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
• Journal: Blood (Blood) Vol. 112 Issue 5 Pg. 1923-30 (Sep 01 2008) ISSN: 1528-0020 [Electronic] United States
• PMID: 18577710 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Biomarkers, Tumor
• Membrane Glycoproteins
• ZAP-70 Protein-Tyrosine Kinase
• CD38 protein, human
• ADP-ribosyl Cyclase 1

Topics

• ADP-ribosyl Cyclase 1 (metabolism)
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics, metabolism)
• Cohort Studies
• Female
• Genes, Immunoglobulin Heavy Chain
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (genetics, immunology, metabolism)
• Male
• Membrane Glycoproteins (metabolism)
• Middle Aged
• Mutation
• Prognosis
• Risk Factors
• ZAP-70 Protein-Tyrosine Kinase (metabolism)