CYTOGENETICALLY ABERRANT CELLS ARE PRESENT IN THE CD34(-)38(-)19(-) MARROW COMPARTMENT IN CHILDREN WITH ACUTE LYMPHOBLASTIC-LEUKEMIA()CD33()

Acute lymphoblastic leukemia (ALL), the most common cancer in childhoo d, is characterized by clonal proliferation of transformed lymphoblast s that comprise the majority of marrow and/or blood specimens. althoug h the leukemic cells typically express antigens associated with lympho id maturation or activation (ie CD19, CD38, etc), it has been suggeste d that ALL blasts may evolve from a more primitive precursor. Increase d understanding of the phenotypic and molecular heterogeneity of cells in ALL may provide clues to leukemogenesis and or impact prognosticat ion or treatment. We utilized a phenotype/genotype approach to measure the prevalence and frequency of cytogenetically aberrant cells in a p henotypically defined primitive compartment (CD34(+)33(-)19(-)38(-); C D33(+)Lin(-)). Bone marrow cells were flow cytometrically sorted into CD34(-)Lin(+), CD34(-)Lin(+) and CD34(+)Lin(-) subpopulations. Fluores cence in situ hybridization (FISH) was used to quantify the frequency of cells with aneusomies in the sorted populations. Approximately 26% (5/19) of ALL cases at diagnosis contain cytogenetically aberrant CD34 (+)Lin(-) cells. The frequency of cytogenetically aberrant cells In th e CD34(+)Lin(-) compartment is independent of FAB, WBC and blast count s, These data indicate that cytogenetically aberrant cells may reside in a phenotypically defined primitive subpopulation and suggest that A LL blasts in some patients may evolve from a precursor compartment.