Phenotypic heterogeneity in acute leukemia

Abstract

Although neoplastic hematopoietic cells usually display a phenotype consistent with some stage of normal development, a significant number of leukemia cases express a combination of cell surface and other markers rarely found in normal cells. Many terms have been used to describe atypical leukemia phenotypes (lineage infidelity, lineage promiscuity, biphenotypic, biclonal, hybrid, bilineal, mixed lineage differentiation, asynchronous differentiation). Some of these terms presume knowledge of mechanisms of atypical marker expression or of the clonal origin of leukemic cells, information which is often not available in individual patients. It may be simpler to categorize atypical leukemic differentiation as being of two types: mixed lineage differentiation and asynchronous differentiation. In mixed lineage differentiation one or more markers from two or more different lineages are expressed in leukemic cells. In asynchronous differentiation the markers expressed are lineage appropriate, but are not expressed in the proper combination. In either situation, there may be significant heterogeneity among leukemic cells from an individual patient. Mixed lineage differentiation in patients (reviewed by Gale and Bassat [ 11) may be expressed in several forms, e.g. hybrid leukemia (two separate clones; very rare), biphenotypic leukemia (> 10% of cells express markers from more than one lineage simultaneously), bilineal leukemia (single cells displaying either one or the other phenotype). Bilineal leukemia can be synchronous (both populations at the same time) or metachronous (one population following another in time; i.e. ‘lineage switch’ [2]). Because the clinical consequences of these different forms of mixed lineage differentiation are not clear and in many cases it is difficult to differentiate among them, for the purposes of this review they are considered together as examples of mixed lineage differentiation.