A surrogate marker profile for PML/RAR alpha expressing acute promyelocytic leukemia and the association of immunophenotypic markers with morphologic and molecular subtypes.
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.
Paietta
E
E
Immunology Laboratory, Our Lady of Mercy Cancer Center, New York Medical College, Bronx, New York 10466, USA. epaietta@earthlink.net
Goloubeva
O
O
Neuberg
D
D
Bennett
J M
JM
Gallagher
R
R
Racevskis
J
J
Dewald
G
G
Wiernik
P H
PH
Tallman
M S
MS
D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000276:immunology; D002869:Chromosome Aberrations; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis / Q000276:immunology; D009687:Nuclear Proteins / Q000032:analysis / Q000276:immunology; D015514:Oncogene Proteins, Fusion / Q000032:analysis / Q000276:immunology; D011237:Predictive Value of Tests; D000071156:Promyelocytic Leukemia Protein; D018168:Receptors, Retinoic Acid / Q000032:analysis / Q000276:immunology; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors / Q000032:analysis / Q000276:immunology; D025521:Tumor Suppressor Proteins
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D000071156:Promyelocytic Leukemia Protein; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human