FLOW CYTOMETRIC DIAGNOSIS OF THE CELL LINEAGE AND DEVELOPMENTAL STAGEOF ACUTE LYMPHOBLASTIC-LEUKEMIA BY NOVEL MONOCLONAL-ANTIBODIES SPECIFIC TO HUMAN PRE-B-CELL RECEPTOR

Three novel monoclonal antibodies (MoAbs) have been established that r ecognize distinct epitopes of a human pre-B-cell receptor (pre-BCR) co mposed of a mu heavy (mu H) chain and a lambda 5/VpreB surrogate light (SL) chain. HSL11 react's with lambda 5 whereas HSL96 reacts with Vpr eB, Intriguingly, HSL2 does not bind to each component of the pre-BCR but does bind to the completely assembled pie-BCR complex. Flow cytome tric analyses with cytoplasmic staining of a panel of human cell lines showed that HSL11 and HSL96 specifically stained cell lines derived f rom the pro-B and pre-B-cell stages of B-cell development. In contrast , HSL2 stained exclusively cell lines derived from the pre-B-cell stag e. These results prompted us to explore the possibility of clinical ap plication of these MoAbs for the determination of the cell lineage and developmental stage of acute lymphoblastic leukemia (ALL). Whereas no ne of mature B-lineage ALLs (B-ALLs), T-lineage ALLs (T-ALLs), and acu te myeloid leukemias analyzed were stained in the cytoplasm with these three MoAbs, the vast majority of non-B- and non-T-ALLs (53 out of 56 cases) were found positive for either lambda 5, Vpre-B, or both in th eir cytoplasm. Among these 53 cytoplasmic SL chain-positive ALLs, 19 c ases were also positive for cytoplasmic pH chain, indicative of pre-B- cell origin. Interestingly 6 out of these 19 pre-B-ALL cases were foun d negative for cytoplasmic staining with HSL2. From these results, we propose a novel classification of,B-ALL in which five subtypes are def ined on the basis of the differential expression of SL chain, mu H cha in, pre-BCR, and light chain along the B-cell development. (C) 1998 by The American Society of Hematology.