ZAP-70 and Bcl-2 expression in B lymphoblastic leukemia cells and hematogones.
BACKGROUND
Flow cytometric immunophenotyping has an established role in the diagnosis and monitoring of B-lymphoblastic leukemia (B-LL). However, the search continues for an optimal reagent set that can identify leukemic blasts with specificity, reproducibility, and sensitivity, at any point during the course of the disease and in every specimen type.


METHODS
This study evaluated the diagnostic utility of detecting the intracytoplasmic antigens zeta-associated protein (ZAP-70) and Bcl-2 in the distinction between the leukemic blasts of B-LL and hematogones.


RESULTS
In comparison with hematogones in reference specimens, significantly higher levels of Bcl-2 were identified in 21 of 23 (91%) B-LL. In particular, Bcl-2 expression was consistently higher in leukemic blasts with bright intensity CD10 expression than the equivalent most immature (CD10 bright intensity) hematogones. As previously reported, Bcl-2 expression was lower in B-LL with BCR-ABL1 gene rearrangement, but the fluorescence intensity of this group of specimens was still significantly higher than that seen for hematogones. In contrast, ZAP-70 was expressed at significantly higher levels in only 7 of 23 (30%) B-LL and demonstrated other findings that might limit clinical utility, including differences in the level of ZAP-70 expression during therapy and between blasts in the peripheral blood and bone marrow.


CONCLUSIONS
Bcl-2 over-expression provides a useful tool for the distinction between B-LL and hematogones. In contrast, although further optimization of the ZAP-70 assay might increase the sensitivity of detection, over-expression of ZAP-70 was identified in only a minority of B-LL.
Division of Hematopathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. craigfe@upmc.edu
Fiona E
FE
Craig
Sara A
SA
Monaghan
Urvashi
U
Surti
Steven H
SH
Swerdlow
D000293:Adolescent; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000473:pathology; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007223:Infant; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D055815:Young Adult; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000096:biosynthesis* / Q000097:blood*
D019253:Proto-Oncogene Proteins c-bcl-2; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human