We have characterixed a transcription unit at chromosome band 19p13 that lies at the site of a chromosomal transiocation breakpoint in T ceil acute iymphobiastic leukemia. The/y/-l gene is structurally altered foiiowing a tnl9) transiocation, resulting in its head-tohead juxtaposition with the T ceil receptor CP gene and truncation of/y/-l RNA. The predicted protein product of the/y/-l gene contains a potential heiixloop-helix DNA binding motif also found in several proteins involved in the control of cellular proliferation and differentiation: ail members of the Myc family, MyoDl, myogenin, the Dmsophiia achaefe-scufe, twist, and daughterless proteins, and two recently described immunogiobulln enhancer binding proteins. The implication of Lyi-1 in cellular transformation suggests that other proteins containing similar DNA binding motifs may also be lmrolved with neoplastic transformation in various cellular lineages. introduction

Chromosomal transiocations have been clearly demonstrated to be important pathogenetic events in human hematolymphoid malignancies. The best-studied exampies are transiocations involving the c-myc gene in Burkitt’s lymphomas and those affecting c-abl in acute and chronic ieukemias. These studies have established an important paradigm whereby cellular genes involved in the control of proliferation and/or differentiation may be converted to oncogenic forms by certain chromosomai events that alter their structure or expression. However, in the majority of hematoiymphoid malignancies the myc and abl genes are apparently uninvolved, and this has led to the search for additional, uncharacterized genetic loci that may be important for induction or maintenance of the transformed phenotype.