Fine characterization of childhood and adult acute lymphoblastic leukemia (ALL) by a proB and preB surrogate light chain-specific mAb and a proposal for a new B cell ALL classification

The expression of the surrogate light chain (PsiL)- made of the lambda -lik e (or lambda5) and the VpreB proteins - is a B cell-specific maturation mar ker. Using an anti-human VpreB mAb (4G7), we recently identified in human n ormal bone marrows, proB and preB cells that express the PsiH-PsiL proB (pr oBCR) and the mu-PsiL preB (preBCR) receptors, respectively. In the present study, FAGS and biochemical analysis confirm the broad proB and preB react ivity of the 4G7 mAb that contrasts with the narrow specificity of other av ailable anti-PsiL reagents for preB cells. This mAb was used to explore int racytoplasmic and cell surface expression of the VpreB protein on a series of 92 precursor B cell ALLs (from 40 child and 52 adult patients), in combi nation with 24 other mAbs. The major result concerns the identification wit hin proB (or BI) and common (or BII) ALLs, of proBCR(-) and proBCR(+) ALLs that express the VpreB in the cytoplasm or at the cell surface, respectivel y. The percentage of ALLs within these two VpreB sub-groups differ consider ably between the ALL origin. In the pediatric series, ALLs present in the m ajority a proBCR(+) phenotype whereas we observed a proBCR- phenotype for a dult ALLs. Based on VpreB expression, and in combination with other publish ed data, we propose a refined classification for precursor B cell ALLs.