Modulation of antigen expression in B-cell precursor acute lymphoblastic leukemia during induction therapy is partly transient: evidence for a drug-induced regulatory phenomenon. Results of the AIEOP-BFM-ALL-FLOW-MRD-Study Group.
BACKGROUND
Changes of antigen expression on residual blast cells of acute lymphoblastic leukemia (ALL) occur during induction treatment. Many markers used for phenotyping and minimal residual disease (MRD) monitoring are affected. Glucocorticoid (GC)-induced expression modulation has been causally suspected, however, subclone selection may also cause the phenomenon.


METHODS
We investigated this by following the phenotypic evolution of leukemic cells with flow cytometry from diagnosis to four time points during and after GC containing chemotherapy in the 20 (of 360 consecutive) B-cell precursor patients with ALL who had persistent MRD throughout.


RESULTS
The early expression changes of CD10 and CD34 were reversible after stop of GC containing chemotherapy. Modulation of CD20 and CD45 occurred mostly during the GC phase, whereas CD11a also changed later on. Blast cells at diagnosis falling into gates designed according to "shifted" phenotypes from follow-up did not form clusters and were frequently less numerous than later on.


CONCLUSIONS
Our data support the idea that drug-induced modulation rather than selection causes the phenomenon. The good message for MRD assessment is that modulation is transient in at least two (CD10 and CD34) of the five prominent antigens investigated and reverts to initial aberrant patterns after stop of GC therapy, whereas CD20 expression gains new aberrations exploitable for MRD detection.
Dworzak
Michael N
MN
Laboratory of Immunological Diagnostics, Children's Cancer Research Institute, Vienna, Austria. michael.dworzak@ccri.at
Gaipa
Giuseppe
G
Schumich
Angela
A
Maglia
Oscar
O
Ratei
Richard
R
Veltroni
Marinella
M
Husak
Zvenyslava
Z
Basso
Giuseppe
G
Karawajew
Leonid
L
Gadner
Helmut
H
Biondi
Andrea
A
D000293:Adolescent; D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology
D015703:Antigens, CD; D005938:Glucocorticoids