Flow cytometry is widely used for leukemia diagnosis and is suitable for routine minimal residual disease (MRD) assays. In childhood ALL flow cytometry and PCR can be highly concordant. MRD detection by flow cytometry is based on the identification of leukemia-associated immunophenotypes (LAIPs), which are not expressed by normal bone marrow (BM) or peripheral blood cells. While T-ALL blasts normally express nuclear TdT/cytoplasmic CD3 in more than 90% of cases, B-lin- eage ALL blasts usually share most phenotypes of normal BM B-cell pre- cursors. Thus, the identification of LAIPs requires first that the phenotypic profiles of normal cells are fully characterized. LAIPs can be cur- rently identified in 95% of childhood ALL cases. Fewer studies have addressed the feasibility, sensitivity, reproducibility, and prognostic significance of flow cytometric MRD detection in adult ALL. A flow cyto- metric approach to minimal residual disease (MRD) monitoring useful in childhood B-lineage acute lymphoblastic leukemia (ALL) is here dis- cussed in the context of ALL in adults. We characterized adult normal BM B-cell precursors and compared the marker combinations to those expressed by adult B-lineage ALL blasts. Then, we assessed the expression stability of the identified phenotypes, and eventually the potential prognostic significance of MRD monitoring with these phenotypes. Of 64 leukemia samples analyzed, 95.3% had at least one abnormal phenotype (two or more in 57.3%) as compared to physiologic B-cell precursors in adult bone marrow. The sensitivity of the method was 1 leukemic cell among 10,000 normal cells in 16/19 experiments (84.2%). Blast phenotypes were stable in culture and at relapse, and were useful for MRD monitoring in patients. We conclude that marker combinations for childhood ALL are also applicable to adult cases.
METHODOLOGICAL APPROACH TO MINIMAL RESIDUAL DISEASE DETECTION BY FLOW CYTOMETRY IN ADULT B-LINEAGE ACUTE LYMPHOBLASTIC LEUKEMIA
KRAMPERA, Mauro;PERBELLINI, Omar;PASINI, Annalisa;SCUPOLI, Maria;PIZZOLO, Giovanni
2006-01-01
Abstract
Flow cytometry is widely used for leukemia diagnosis and is suitable for routine minimal residual disease (MRD) assays. In childhood ALL flow cytometry and PCR can be highly concordant. MRD detection by flow cytometry is based on the identification of leukemia-associated immunophenotypes (LAIPs), which are not expressed by normal bone marrow (BM) or peripheral blood cells. While T-ALL blasts normally express nuclear TdT/cytoplasmic CD3 in more than 90% of cases, B-lin- eage ALL blasts usually share most phenotypes of normal BM B-cell pre- cursors. Thus, the identification of LAIPs requires first that the phenotypic profiles of normal cells are fully characterized. LAIPs can be cur- rently identified in 95% of childhood ALL cases. Fewer studies have addressed the feasibility, sensitivity, reproducibility, and prognostic significance of flow cytometric MRD detection in adult ALL. A flow cyto- metric approach to minimal residual disease (MRD) monitoring useful in childhood B-lineage acute lymphoblastic leukemia (ALL) is here dis- cussed in the context of ALL in adults. We characterized adult normal BM B-cell precursors and compared the marker combinations to those expressed by adult B-lineage ALL blasts. Then, we assessed the expression stability of the identified phenotypes, and eventually the potential prognostic significance of MRD monitoring with these phenotypes. Of 64 leukemia samples analyzed, 95.3% had at least one abnormal phenotype (two or more in 57.3%) as compared to physiologic B-cell precursors in adult bone marrow. The sensitivity of the method was 1 leukemic cell among 10,000 normal cells in 16/19 experiments (84.2%). Blast phenotypes were stable in culture and at relapse, and were useful for MRD monitoring in patients. We conclude that marker combinations for childhood ALL are also applicable to adult cases.
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