title: Drug-induced immunophenotypic modulation in childhood ALL: implications for minimal residual disease detection.
abstract: Assessment of minimal residual disease (MRD) by flow cytometry is considered to be based on the reproducibility of the leukemic immunophenotype detected at diagnosis. However, we previously noticed modulation of surface antigen expression in acute lymphoblastic leukemia (ALL) during the early treatment. Hence, we investigated this in 30 children with B-cell precursor ALL consecutively enrolled in the AIEOP-BFM ALL 2000 protocol. Quantitative expression of seven antigens useful in MRD monitoring was studied at diagnosis and compared to that measured at different time points of remission induction therapy. Downmodulation in the expression of CD10 and CD34 occurred at follow-up. By contrast, upmodulation of CD19, CD20, CD45RA, and CD11a was observed, while the expression of CD58 remained stable. Despite this, we could unambiguously discriminate leukemic cells from normal residual B cells. This holds true when bone marrow (BM) samples from similarly treated T-ALL patients, but not from healthy donors, were used as reference. Our results indicate that immunophenotypic modulation occurs in ALL during the early phases of BFM-type protocols. However, the accuracy of MRD detection by flow cytometry seems not negatively affected if adequate analysis protocols are employed. Investigators should take this phenomenon into account in order to avoid pitfalls in flow cytometric MRD studies.
authors.affiliation: Centro Ricerca M Tettamanti, Clinica Pediatrica Università Milano-Bicocca, Ospedale San Gerardo, Via Donizetti 106, 20052 Monza, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Gaipa
authors.forename: G
authors.initials: G
authors.lastname: Basso
authors.forename: O
authors.initials: O
authors.lastname: Maglia
authors.forename: V
authors.initials: V
authors.lastname: Leoni
authors.forename: A
authors.initials: A
authors.lastname: Faini
authors.forename: G
authors.initials: G
authors.lastname: Cazzaniga
authors.forename: C
authors.initials: C
authors.lastname: Bugarin
authors.forename: M
authors.initials: M
authors.lastname: Veltroni
authors.forename: B
authors.initials: B
authors.lastname: Michelotto
authors.forename: R
authors.initials: R
authors.lastname: Ratei
authors.forename: T
authors.initials: T
authors.lastname: Coliva
authors.forename: M G
authors.initials: MG
authors.lastname: Valsecchi
authors.forename: A
authors.initials: A
authors.lastname: Biondi
authors.forename: M N
authors.initials: MN
authors.lastname: Dworzak
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D002648:Child; D015331:Cohort Studies; D006801:Humans; D016130:Immunophenotyping; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology* / Q000628:therapy; D012074:Remission Induction
chemical_list: D015703:Antigens, CD