COMPARATIVE PHENOTYPE MAPPING OF NORMAL VS. MALIGNANT PEDIATRIC B-LYMPHOPOIESIS UNVEILS LEUKEMIA-ASSOCIATED ABERRATIONS

Leukemic cells of B-lineage acute lymphoblastic leukemia (ALL) are reg arded as the malignant counterparts of immature, physiologic B cell pr ecursors (BCPs). To determine whether phenotypic differences exist bet ween these corresponding cell types, we investigated samples of normal pediatric bone marrow (n=30) as well as of B-precursor ALL at diagnos is (n=53; common and pre-B subtype). Using three-color multiparameter flow cytometric analysis, we compared the leukemic populations with th e physiologic BCPs of corresponding maturity with respect to the inten sity with which they expressed a series of antigens. In some of these antigens, leukemia-associated aberrations were frequently observed. In particular, overexpression of CD10 was displayed by 65% of ALL sample s, whereas 58% of leukemic cases aberrantly exhibited very low or no C D45RA expression. Regarding CD11a and CD44, 47% and 35% of ALL populat ions were aberrant as defined by either the absence or significant ove rexpression of the antigen. In contrast, antigen densities of CD49d, C D49e, and CD99 on leukemic cells were in the normal range of values fo r BCPs. Combining the patterns of frequently aberrant markers in a com prehensive analysis, we were able to identify individual phenotypic le ukemic cell aberrations in up to 98% of investigated cases. CD10 and/o r CD45RA were aberrant in 86% of cases overall, emphasizing the high d iscriminative potential of these two markers. Using comparative phenot ype mapping based on quantitatively aberrant, leukemia-associated anti genic patterns, we were able to detect leukemic blasts among normal bo ne marrow cells at frequencies as low as 10(-5). We speculate that our approach may have a profound impact on the development of new strateg ies for minimal residual disease investigations in patients with BCP-A LL.