Surface Immunoglobulin Light Chain Expression in Pre-B Cell Leukemia9 z BENJAMIN KOZINER, JANET STAVNEZER, ABRAHAM MITTELMAN, MICHAEL ANDREEFF, AND BAYARD D. CLARKSON zyx Memorial Sloan Kettering Cancer Center zyx New York, New York zyxw 10021 AYAD AL-KATIB, DAVID GEBHARD, INTRODUCTION Our understanding of cellular differentiation is being rapidly increased by the development of monoclonal antibodies and by modem techniques of molecular genetic analysis. In particular, our knowledge of the phenotype, i.e. the cell lineage and state of differentiation, of acute lymphoblastic leukemia (ALL) and the blastic phase of chronic myelogenous leukemia (BL-CML) are undergoing revision. Most cases of ALL have lymphoblasts that were thought to fall into the non-B, non-T (“null”) category, but have recently been shown to be within the B- cell differentiative compartment. An early study, using cytoplasmic immuno- globulin (cIg) zyxwvu p heavy chain expression as a marker for pre-B-cells, indicated that approximately 18% of “null” ALL cases were of the pre-B phenotype, i.e. they expressed cIg p chain but did not express surface immunoglobulin (sIg).’ Monoclonal antibodies raised by immunizing mice with pre-B-cell lines have been useful in further elucidating the B-cell lineage of some ALL cases. Both B1* and BA2: which are pre-B cell markers defined by such monoclonal antibodies, have been clearly demonstrated on ALL cells. Moreover, analysis of immuno- globulin (Ig) gene rearrangements in ALL cells conclusively showed a commit- ment to the B-cell pathway in all 25 cases that were e~amined.4~ It has recently been reported that the leukemic cells from a patient with null “common” ALL were induced to proceed along the B-differentiative pathway so as to acquire a B- associated antigen (BA2).5 These cells showed decreased expression of terminal deoxynucleotidyl transferase (TdT) and expressed cIg and ultimately sIg. Similarly to ALL, about one-third of patients with BL-CML have been found to have leukemic cells with pre-B lymphoid characteristics. Cytoplasmic p chain, but not sIg, has been detected in the blast cells from some patients with BGCML6 who also expressed high levels of TdT and were positive for the Philadelphia chromosome. Ig heavy chain genes were rearranged in BL-CML cells from seven and Ig light chain genes were rearranged in three of eight patients examined by Bakhshi et a1.2 providing further evidence of their commitment to differentiate along the B-cell lineage. “This work was parly supported by grants CA-08748, CA-20194, CA-05826, CA-29564 from the National Cancer Institute, and AI 17558 from the National Institutes of Health. z 211