Identification of residual leukemic cells by flow cytometry in childhood B-cell precursor acute lymphoblastic leukemia - Verification of leukemic state by flow-sorting and molecular/cytogenetic methods

TY - JOUR

T1 - Identification of residual leukemic cells by flow cytometry in childhood B-cell precursor acute lymphoblastic leukemia - Verification of leukemic state by flow-sorting and molecular/cytogenetic methods

AU - Obro, Nina Friesgaard

AU - Ryder, Lars Peter

AU - Madsen, Hans Ole

AU - Andersen, Mette Klarskov

AU - Lausen, Birgitte

AU - Hasle, Henrik

AU - Schmiegelow, Kjeld

AU - Marquart, Hanne Vibeke

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Reduction in minimal residual disease, measured by real-time quantitative PCR or flow cytometry, predicts prognosis in childhood B-cell precursor acute lymphoblastic leukemia. We explored whether cells reported as minimal residual disease by flow cytometry represent the malignant clone harboring clone-specific genomic markers (53 follow-up bone marrow samples from 28 children with B-cell precursor acute lymphoblastic leukemia). Cell populations (presumed leukemic and non-leukemic) were flow-sorted during standard flow cytometry-based minimal residual disease monitoring and explored by PCR and/or fluorescence in situ hybridization. We found good concordance between flow cytometry and genomic analyses in the individual flow-sorted leukemic (93% true positive) and normal (93% true negative) cell populations. Four cases with discrepant results had plausible explanations (e.g. partly informative immunophenotype and antigen modulation) that highlight important methodological pitfalls. These findings demonstrate that with sufficient experience, flow cytometry is reliable for minimal residual disease monitoring in B-cell precursor acute lymphoblastic leukemia, although rare cases require supplementary PCR-based monitoring.

AB - Reduction in minimal residual disease, measured by real-time quantitative PCR or flow cytometry, predicts prognosis in childhood B-cell precursor acute lymphoblastic leukemia. We explored whether cells reported as minimal residual disease by flow cytometry represent the malignant clone harboring clone-specific genomic markers (53 follow-up bone marrow samples from 28 children with B-cell precursor acute lymphoblastic leukemia). Cell populations (presumed leukemic and non-leukemic) were flow-sorted during standard flow cytometry-based minimal residual disease monitoring and explored by PCR and/or fluorescence in situ hybridization. We found good concordance between flow cytometry and genomic analyses in the individual flow-sorted leukemic (93% true positive) and normal (93% true negative) cell populations. Four cases with discrepant results had plausible explanations (e.g. partly informative immunophenotype and antigen modulation) that highlight important methodological pitfalls. These findings demonstrate that with sufficient experience, flow cytometry is reliable for minimal residual disease monitoring in B-cell precursor acute lymphoblastic leukemia, although rare cases require supplementary PCR-based monitoring.

U2 - 10.3324/haematol.2011.051383

DO - 10.3324/haematol.2011.051383

M3 - Journal article

C2 - 21933850

SN - 0390-6078

VL - 97

SP - 137

EP - 141

JO - Haematologica

JF - Haematologica

IS - 1

ER -