Constitutive expression of CD26/dipeptidylpeptidase IV on peripheral blood B lymphocytes of patients with B chronic lymphocytic leukaemia

Abstract

SummaryWe have investigated the expression of the ectoenzyme dipeptidylpeptidase IV (DPP IV)/CD26 on lymphocytes obtained from patients with B chronic lymphocytic leukaemia (B-CLL) and compared it with healthy subjects. Using two-colour immunofluorescence analysis with CD26 and CD20 or CD23 monoclonal antibodies, CD26 was found undetectable on peripheral resting B-cells (CD20 + CD23 -) from normal donors whereas it was expressed on B-cells activated in vitro with interleukin (IL)-4 and Staphylococcus aureus strain cowan I (CD20 + CD23 + ). The expression of CD26 on leukaemic B-cells (CD20 + CD23 + ) was clearly induced in 22 out of 25 patients examined. Consequently, induced levels of CD26 cell surface expression on either normal activated and malignant B-cells coincided with the enhancement of DPP IV activity detected on the surface of these cells. Reverse transcription polymerase chain reaction analyses showed that the transcript levels of the CD26 gene was higher in normal activated B-cells and B-CLL cells than in resting B-cells, suggesting that CD26 was expressed at the level of transcriptional activation. These observations provide evidence of the abnormal expression of DPPIV/CD26 in B-CLL which, therefore, may be considered as a novel marker for B-CLL. Further investigation in relation to CD26 expression and other B malignancies needs to be defined.

Regulation of CD26/DPPIV gene expression by interferons and retinoic acid in tumor B cells

“…One of these ectoenzymes, dipeptidylpeptidase IV (DPPIV) assigned to CD26, may be considered as a useful marker in some diseases. Overexpression of CD26 is observed in dierentiated thyroid (Tanaka et al, 1995) and liver (Stecca et al, 1997) carcinoma, on blood T cells from patients with autoimmune diseases (Ha¯er et al, 1985;Eguchi et al, 1989;Nakao et al, 1989) and in B cell chronic lymphocytic leukemia (B-CLL) (Bauvois et al, 1999). In contrast, the loss of CD26 has been associated with T-CLL and ALL (Kondo et al, 1996) and melanoma progression (Wesley et al, 1999).…”

“…Intact cells were immunostained as previously described (Bauvois et al, 1999). Cells were permeabilized by ®xing in 4% formaldehyde containing 50% EtOH for 10 min at room temperature.…”

“…IL-4 and Il-13 stimulate the expression of CD26 on human renal cell carcinoma and renal tubular epithelial cells (Riemann et al, 1995). In the B lineage, CD26 is induced on human resting B lymphocytes during their in vitro activation with Staphylococcus aureus cowan I protein and IL-4 (BuÈ hling et al, 1994;Bauvois et al, 1999). Consequently, little is known about the regulation of CD26 in B lineage cells and increased knowledge about the regulation of CD26 in B-CLL may be of clinical interest.…”

Effect of CD26/dipeptidyl peptidase IV on Jurkat sensitivity to G2/M arrest induced by topoisomerase II inhibitors

“…Additionally, its DPPIV enzyme activity has a key role in various aspects of T-cell activation, as demonstrated by studies using DPPIV inhibitors, soluble CD26/DPPIV molecules or CD26 genetic mutants (Flentke et al, 1991;Tanaka et al, 1993Tanaka et al, , 1994Steinbrecher et al, 2001). Besides its involvement in normal T-cell function, CD26 may also have a role in the development of certain tumors (Tanaka et al, 1995;Stecca et al, 1997;Bauvois et al, 1999;Dang and Morimoto, 2002). For example, it is expressed on the surface of such aggressive T-cell malignancies as T-cell lymphoblastic lymphomas/ acute lymphoblastic leukaemias and T cell CD30+ anaplastic large cell lymphomas, but not on the more indolent T-cell diseases like mycosis fungoides (Carbone et al, 1995;Jones et al, 2001).…”

CD26/dipeptidyl peptidase IV enhances expression of topoisomerase II alpha and sensitivity to apoptosis induced by topoisomerase II inhibitors

“…Meanwhile, recent findings suggest that CD26 has a role in the development of certain types of neoplasms (Morrison et al, 1993;Sedo and Revoltella, 1995;Tanaka et al, 1995;Stecca et al, 1997). B-chronic lymphocytic leukaemia cells have high levels of CD26 protein expression and mRNA transcripts (Bauvois et al, 1999); whereas the more aggressive T-cell malignancies, such as T-cell acute lymphoblastic leukaemia or T-cell CD30 þ anaplastic large-cell lymphoma, express higher CD26 level as compared to the more indolent Tcell diseases like mycosis fungoides (Carbone et al, 1995;Jones et al, 2001).…”