A Surrogate Marker Profile for PML/RARα Expressing Acute Promyelocytic Leukemia and the Association of Immunophenotypic Markers with Morphologic and Molecular Subtypes

Background: The availability of genotype-specific therapy for PML/RARα^pos acute promyelocytic leukemia (APL) requires that this disease be precisely diagnosed. Immunophenotypic characteristics heretofore proclaimed as reliably characterizing APL (HLA-DR^low, CD34^low, P-glycoprotein^low myeloid phenotype) do not differentiate from APL-like immune profiles unassociated with the PML/ RARα fusion transcript. Methods: To establish a surrogate marker profile for APL, we explored 19 potentially predictive markers compared with differentiated acute myeloid leukemia using the classification tree approach with recursive partitioning. Results: In a test group of 58 APL patients, the most predictive immune profile was HLA-DR^low, CD11a^low (α_L subunit of the leukocyte integrin LFA-1), CD18 ^low (β₂ subunit of LFA-1). APL cells always expressed CD117 (c-kit) but lacked the progenitor antigen CD133 and the more mature myeloid antigen, CD11b (α_M leukocyte integrin). This antigen pattern was validated in 90 additional APL patients. M3v APLs (n = 30) had more leukemic promyelocytes expressing the T-cell antigen, CD2 (P < 0.0001) or the stem cell marker, CD34 (P = 0.0003) and demonstrated higher fluorescence intensity for the binding of antibody to the common leukocyte antigen, CD45 (P = 0.0008) than M3 (n = 102). S-form APL (n = 45) had a higher percent of cells expressing CD2 or CD34 (P < 0.0001 for both) or the neural cell adhesion molecule CD56 (P = 0.001) than L-form APL (n = 66). Conclusions: PML/RARα^pos APL cells typically lack leukocyte integrins. HLA-DR^low, CD11a^low, CD18^low is a reliable surrogate antigen expression profile for PML/RARα^pos APL, irrespective of morphology and transcript isoform.