Human acute unclassified leukemia with a unique t(4;17) chromosomal translocation expresses T lymphoid and myeloid surface antigens after in vitro culture

Abstract

Bilineage differentiation along both the T lymphoid and the myeloid lineage while in in vivo diffusion chamber (DC) and in vitro suspension culture was observed in a case of acute unclassified leukemia (null-AL) and t(4;17). Prior to culture, the blast cells were TdT and la positive but did not express any lineage-specific antigenic markers. Furthermore, the immunoglobulin heavy chain and T cell receptor beta-chain genes were in germline configuration. Cytogenetically, all metaphases had the unique translocation t(4;17) (q25;q23) prior to and after culture, supporting the leukemic origin of the cells. During both DC culture and suspension culture with and without tetradecanoyl-phorbol-acetate (TPA), a substantial increase in the absolute and relative number of cells expressing both myeloid and T lymphoid antigenic markers occurred. Double-fluorescence analysis demonstrated the expression of antigenic markers of both lineages on the same population of cells, and electron microscopy revealed the induction of myeloperoxidase after both DC and suspension culture. Immunoglobulin heavy chain and T cell receptor beta-chain genes remained in germline configuration after treatment with TPA, when analyzed with JH and CT beta probes, respectively. These findings indicate that this case represents a null-AL with dual-lineage capabilities, which has probably arisen from the malignant transformation of a bipotential stem cell of lymphoid and myeloid progeny.