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

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

Research output: Contribution to journalArticle

243 Scopus citations

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. Multivariate 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.

Original languageEnglish (US)
Pages (from-to)1923-1930
Number of pages8
JournalBlood
Volume112
Issue number5
DOIs
StatePublished - Sep 1 2008

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Rassenti, L. Z., Jain, S., Keating, M. J., Wierda, W. G., Grever, M. R., Byrd, J. C., Kay, N. E., Brown, J. R., Gribben, J. G., Neuberg, D. S., He, F., Greaves, A. W., Rai, K. R., & Kipps, T. J. (2008). Relative value of ZAP-70, CD38, and immunoglobulin mutation status in predicting aggressive disease in chronic lymphocytic leukemia. Blood, 112(5), 1923-1930. https://doi.org/10.1182/blood-2007-05-092882