The Prognostic Value of CD38 Expression and its Quantification in B Cell Chronic Lymphocytic Leukemia (B-CLL)

Abstract

A large number of prognostic factors are available to help predict the outcome of patients who present with B-cell chronic lymphocytic leukemia (B-CLL). These include clinical stage, leukemic cell morphology, lymphocyte doubling time, the pattern of infiltration in bone marrow trephine biopsies, cytogenetic abnormalities, p53 function and serum factors such as beta-2 microglobulin. Two recently described major prognostic factors are immunoglobulin heavy chain variable region (IgVH) mutation status and cell membrane expression of CD38. These are both highly significant independent prognostic factors, but are not closely correlated. Whereas IgVH mutational status is a time consuming and demanding technique, only available in a limited number of centres, CD38 expression by flow cytometry is relatively simple and rapidly obtained in most diagnostic laboratories. The predictive value of CD38 expression is enhanced by measurement of antigen density in terms of antibody binding capacity (ABC) rather than as the percentage of cells expressing the antigen. ABC correlates closely with relative median fluorescence (RMF), a parameter which is even more simply and cheaply obtained by flow cytometry. One of these methods of determining CD38 expression should be employed routinely. Recent work suggests that membrane ZAP-70 expression determined by flow cytometry will prove to be an accurate proxy for IgVH mutational status and this assay will be within the reach of any laboratory skilled in flow cytometry. The combination of ZAP-70 expression, CD38 antigen density, p53 function and the concentration of serum factors such as soluble CD23, is likely to provide extremely accurate prognostic information in future studies. This will assist in identifying Stage A patients who may benfit from early and/or more intensive treatment, as well as Stage B and C patients who may require alternative treatment strategies at the outset.

B-chronic lymphocytic leukemia chemoresistance involves innate and acquired leukemic side population cells

“…25 Likewise, SP cells from other mature B-cell malignant hemopathies, such as multiple myeloma, also present phenotypes inherent to the differentiation status of their non-malignant counterpart. 21 The increased level of CD38 expression, which here typified B-CLL SP cells from CD38 þ patients, is usually observed for highly proliferating B-CLL cells 29 and correlates with a poor clinical outcome, 30 supporting the view that B-CLL SP cells are important for progression of the disease. The fact that whether in vitro SP cells exposed to pertinent stimuli and microenvironmental cells 31 actually undergo more mitosis than the bulk of quiescent B-CLL cells remains elusive, although likely.…”

ZAP‐70 expression is low in normal precursor B cells or hematogones

“…ZAP-70 and CD38 are independent prognostic factors in diagnosing patients with B-CLL [1,[3][4][5][6][17][18][19][20][21][22][23]. Hematogones have the potential to contribute misleading information to the evaluation of these two important prognostic markers if not excluded from the CLL population during the analysis of flow cytometric data.…”

Isolation of hematopoietic stem cells and the effect of CD38 expression during the early erythroid progenitor cell development process

“…CD38 is a multifunctional ectoenzyme that exhibits NAD glycohydrolase, ADP ribosyl cyclase and ADP ribosyl hydrolase activities. A number of studies indicated that a high level of CD38 expression is a sign of malignancy (14,15). CD38 also has receptor activity in addition to its enzymatic features.…”