To B- or not to B-: A review of lineage switched acute leukemia

Acute leukemia is a heterogeneous disorder of hematologic malignancies composed primarily of hematopoietic precursors that have acquired unregulated self-renewal and proliferation. Hematology classification systems typically divide these neoplasms into lymphoid (B- or T-) and myeloid-lineage subtypes, with therapy dependent upon this distinction. Infrequently, certain acute leukemias may undergo a complete lineage switch at relapse, subsequently complicating the diagnosis and treatment of these recurrent diseases. Transformation from B-lineage to myeloid lineage is the most common switch observed, and is frequently associated with a balanced 11q23 translocation, involving KMT2A. The mechanisms involved in the lineage-switch are unclear, but modern therapies targeting the B-cell-specific marker, CD19, have proven to promote this conversion as one means of treatment escape. Broadly speaking, therapy-mediated selection of alternate lineage-committed subclones derived from the same initial pluripotent progenitors, clonal evolution and reprogramming of lineage-committed blasts, and de novo clonally unrelated leukemias may account for the clinical impression of lineage switched acute leukemia during treatment. This review will explore the phenomenon and potential mechanisms of lineage transformation during the treatment of acute leukemia.