Undifferentiated acute leukemia and lineage infidelity (difficulties in classification and management)

The acute leukemias have been considered to represent a clonal expansion of a malignant transformed hematopoietic progenitor cell with adherence to either the myeloid or lymphoid lineage--"lineage fidelity." Lineage fidelity has been challenged by the demonstration of lineage switching or mixed-lineage leukemias. We describe a 7 year old male who presented with undifferentiated acute leukemia and nasopharyngeal and cervical masses. His blasts had the morphologic appearance of myeloblasts (FAB M1) and were positive solely for the myeloid antigen CD15. He entered a complete remission (CR) with acute nonlymphocytic leukemia therapy. At first relapse he had evidence of mixed-lineage leukemia with B-cell lymphoid and myeloid phenotypes. He again relapsed from a second CR with Burkitt-cell leukemia. Cytogenetic findings showed a consistent 14q+, 17p+ abnormality in the blasts and nasopharyngeal mass. The t(8;14) associated with Burkitt's lymphoma was found in the mass tissue only following passage in the nude mouse. Our patient demonstrates that limitations still exist in our ability to classify acute leukemia. That leukemic transformation occurred in a multipotential progenitor cell leading to undifferentiated leukemia at diagnosis and/or that chemotherapy can influence the genetic programs of leukemic cells leading to the evidence of mixed-lineage leukemia and lineage switching is supported.