A surrogate marker profile for PML/RAR alpha expressing acute promyelocytic leukemia and the association of immunophenotypic markers with morphologic and molecular subtypes

Abstract

Background: The availability of genotype-specific therapy for PML/RAR alpha(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/RAR alpha 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) (alpha(L) subunit of the leukocyte integrin LFA-1), CD18(low) (beta(2) subunit of LFA-1). APL cells always expressed CD117 (c-kit) but lacked the progenitor antigen CD133 and the more mature myeloid antigen, CD11b (alpha(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/RAR alpha(pos) APL cells typically lack leukocyte integrins. HLA-DR(low), CD11a(low), CD18(low) is a reliable surrogate antigen expression profile for PML/RAR alpha(pos) APL, irrespective of morphology and transcript isoform.