Mn. Dworzak et al., COMPARATIVE PHENOTYPE MAPPING OF NORMAL VS. MALIGNANT PEDIATRIC B-LYMPHOPOIESIS UNVEILS LEUKEMIA-ASSOCIATED ABERRATIONS, Experimental hematology, 26(4), 1998, pp. 305-313
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.