Use of Lymphoid Progenitor Cell Assays for a More Detailed Analysis of the Cytogenetic Changes Occurring During Clonal Evolution in Acute Lymphoblastic Leukemia

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Abstract
Karyotypic and immunophenotypic changes during clonal evolution were studied in 5 B-lineage and 5 T-lineage acute lymphoblastic leukemia (ALL) patients using leukemic progenitor cell assays in combination with cytogenetic and immunophenotypic analyses. Cytogenetic studies demonstrated a clonal chromosomal abnormality in 9 of 10 cases analyzed. The use of leukemic progenitor cell assay system revealed a distinct cytogenetic pattern of clonal evolution in 4 of the 7 patients who experienced leukemic relapses. It also made possible the identification of an abnormal clone in 2 patients in whom no analyzable metaphases were found in fresh marrow blasts. The evidence uniquely indicates that, in ALL 1) leukemic progenitor cell assays combined with fresh marrow cytogenetic and immunophenotypic analyses help clarify the sequence of cytogenetic and immunophenotypic changes during clonal evolution, 2:) cytogenetic changes may occur independent of immunophenotypic changes during clonal evolution, 3) immunologically distinct subclones may exist in a cytogenetically uniform blast population, and 4) normal diploid cells in leukemic bone marrow samples may occasionally represent clonal populations of cytogenetically "normal" leukemic blasts with submicroscopic genetic alterations. To our knowledge, this study represents the first application of leukemic progenitor cell assays in the cytogenetic analyses of ALL blasts. The described methodology can be used for further elucidation of clonal evolution in ALL as well as for more detailed analyses of individual leukemic clones derived from ALL patients.