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A surrogate marker profile for PML/RARα expressing acute promyelocytic leukemia and the association of immunophenotypic markers with morphologic and molecular subtypes
Author(s) -
Paietta E.,
Goloubeva O.,
Neuberg D.,
Bennett J. M.,
Gallagher R.,
Racevskis J.,
Dewald G.,
Wiernik P. H.,
Tallman M. S.
Publication year - 2004
Publication title -
cytometry part b: clinical cytometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.646
H-Index - 61
eISSN - 1552-4957
pISSN - 1552-4949
DOI - 10.1002/cyto.b.20001
Subject(s) - acute promyelocytic leukemia , cd34 , stem cell marker , myeloid leukemia , cd38 , antigen , immunology , myeloid , biology , plasmacytoid dendritic cell , cd33 , integrin , stem cell , cancer research , microbiology and biotechnology , cell , dendritic cell , cell culture , retinoic acid , genetics
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 (β 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 (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. © 2004 Wiley‐Liss, Inc.