Hybrid phenotypes and lineage promiscuity in acute leukemia

Clinical data indicate that AL are heterogeneous diseases with variable responsiveness to chemotherapeutic agents. Based on this evidence, the efforts of most investigators are aimed at providing rapid identification of AL features predictive of distinct prognostic outcomes. A considerable number of reagents (including MoAb and molecular probes) available from commercial sources has been widely used for diagnostic purpose, leading to the identification of "inappropriate" antigen expression and to diagnoses of "mixed" AL (M-AL). The latter still lacks adequate definition and identification criteria, but is frequently reported as a novel entity associated with poor clinical outcome. The use of more accurate methodologic approaches, as well as a better elucidation of normal hemopoietic cell characteristics suggest that true M-AL occur quite rarely: the features of normal precursor counterparts are more frequently conserved. "Ectopic" marker expression, however, which should not be interpreted as reflecting lineage infidelity, may in some instances explain different clinical courses in AL patients. Further elucidation of normal stem cell features, and adequate standardization of AL immunophenotyping--to be performed under proper technical conditions--are needed for a better evaluation of M-AL, both in terms of diagnosis and classification, as well as regarding their clinical significance.