CD38 as a prognostic factor in B cell chronic lymphocytic leukaemia (B-CLL): comparison of three approaches to analyze its expression.
BACKGROUND
Increased CD38 expression by leukemic cells has been suggested as an adverse prognostic factor in B-CLL. Several approaches have been proposed to quantify its level of expression by flow cytometry.


METHODS
We compared the use of (i) the percentage of CD38 positive cells, (ii) CD38 antibodies bound per cell (ABC), and (iii) a semi-quantitative method based on the shape of the CD38 histogram, within a cohort of 78 B-CLL patients.


RESULTS
A decreased overall survival was seen with >30% CD38 positivity among B-CLL cells, with CD38 ABC >100, and with bimodal or unimodal, strongly positive CD38 histograms. However, patients with unimodal weakly positive CD38 histograms also showed a significantly reduced survival as did patients with intermediate proportions (i.e. 5-30%) of CD38+ cells. Furthermore, within the group with <5% CD38 positivity among their B-CLL cells, 84% of patients showed prognostically favourable mutated IGVH gene segments and 100% had low ZAP70 gene expression. For 5-30% CD38 positivity, these proportions were 50 and 83%, while for >30% CD38 positivity, these proportion were only 28 and 56%, respectively.


CONCLUSIONS
We found a simple method of quantitation of CD38 expression (i.e., >5% CD38 positivity among B-CLL cells) to be sufficient to identify patients with an unfavourable prognosis. The level of CD38 expression as defined with this method correlated well with the IGVH mutation status and ZAP70 gene expression.
Boonstra
Joke G
JG
Department of Clinical Chemistry, University Medical Center Rotterdam, Daniel den Hoed Cancer Center, The Netherlands. j.boonstra@erasmusmc.nl
van Lom
Kirsten
K
Langerak
Anton W
AW
Graveland
Wilfried J
WJ
Valk
Peter J M
PJ
Kraan
Jaco
J
van 't Veer
Mars B
MB
Gratama
Jan W
JW
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015925:Cryopreservation; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000235:genetics; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D013194:Staining and Labeling; D016019:Survival Analysis; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics
D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D051997:ADP-ribosyl Cyclase 1