Expression of CD58 in normal, regenerating and leukemic bone marrow B cells: implications for the detection of minimal residual disease in acute lymphocytic leukemia.
OBJECTIVE
CD58, a member of the Ig superfamily, is expressed by hematopoietic and non- hematopoietic cells. It has been demonstrated to be over-expressed in precursor-B acute lymphoblastic leukemia (ALL) blasts when compared to in their normal counterparts, suggesting its potential use in the detection of minimal residual disease (MRD) by flow cytometry (FC). To assess the reliability and accuracy of CD58 for this purpose, we studied its expression in a large series of normal and ALL bone marrow (BM) samples using quantitative FC.


METHODS
We studied 180 precursor-B ALL BM samples at diagnosis (8 pro-B, 164 early-B, 8 mature-B ALL) and 123 follow-up BM samples (n=54 at day +15 and n=69 at day +78), as well as 51 normal BM samples and 7 regenerating BM samples from patients with T-ALL at week 12. We used four-color quantitative FC, focusing analysis on CD58 expression. In follow-up samples from day +78, the MRD level was simultaneously evaluated by real time quantitative polymerase chain reaction (RQ-PCR) amplification of antigen receptor genes.


RESULTS
CD58 expression was significantly higher in ALL blasts than in normal B lymphocytes, while no significant differences between regenerating and normal B lymphocytes were observed. CD58 was expressed in 99.4% of the precursor-B ALL cases and 93.5% of these showed over-expression compared to normal. No significant modulation of CD58 expression during remission induction therapy was noted. Finally, 66 (95.6%) of 69 BM samples simultaneously analyzed using both FC and RQ-PCR at day +78 showed concordant results regarding MRD.


CONCLUSIONS
Our results confirm and further evidence the role of CD58 in the diagnosis and monitoring of precursor-B ALL. In particular, we demonstrated its stability and accuracy in MRD detection at clinically relevant time points. These findings indicate that CD58 is a powerful tool for MRD detection in precursor-B ALL.
Veltroni
Marinella
M
Dipartimento di Pediatria, Università di Padova, Padua, Italy.
De Zen
Lucia
L
Sanzari
Maria Colomba
MC
Maglia
Oscar
O
Dworzak
Michael N
MN
Ratei
Richard
R
Biondi
Andrea
A
Basso
Giuseppe
G
Gaipa
Giuseppe
G
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000737:chemistry*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001853:Bone Marrow / Q000502:physiology; D001854:Bone Marrow Cells / Q000737:chemistry*; D018968:CD58 Antigens / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003199:Computer Systems; D005240:Feasibility Studies; D005260:Female; D005434:Flow Cytometry; D015321:Gene Rearrangement; D006801:Humans; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual; D014411:Neoplastic Stem Cells / Q000737:chemistry*; D016133:Polymerase Chain Reaction; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012038:Regeneration / Q000502:physiology*; D012074:Remission Induction
D014408:Biomarkers, Tumor; D018968:CD58 Antigens