HLA-DRneg patients without acute promyelocytic leukemia show distinct immunophenotypic, genetic, molecular, and cytomorphologic characteristics compared to acute promyelocytic leukemia.
BACKGROUND
Loss of HLA-DR and CD34 is a well-known characteristic of malignant promyelocytes in acute promyelocytic leukemia (APL). However, this immunophenotype is not specific for APL. The purpose of this study was to investigate whether further biological characterization of the HLA-DR(neg) acute myeloid leukemia patients would allow more clearly define criteria to separate APL from non-APL patients.


METHODS
Immunophenotyping, cytogenetics, molecular analyses, and cytomorphology were prospectively performed within routine leukemia diagnostics of 800 patients included in different prospective acute myeloid leukemia multicenter trials.


RESULTS
Beside 60 APL, an additional 62 HLA-DR(neg) non-APL patients were identified. The main differential characteristics of HLA-DR(neg) non-APL included high CXCR-4 expression in most patients and almost all leukemia cells, a significantly higher proportion of patients presenting with NPM1 mutations as well as the significant association with cup-like nuclear morphology. The biological distinctness of both leukemia subtypes was further emphasized by the complete absence of aberrant CD2 expression and increased leukocyte and platelet counts in HLA-DR(neg) non-APL patients. Even in the CD34(pos) subgroup of HLA-DR(neg) non-APL all those features contributed in at least the same way to the separation from APL.


CONCLUSIONS
The results of the present study show that an immunophenotypic, molecular, and cytomorphologic separation of both HLA-DR(neg) leukemia subgroups is possible indicating that both groups are biologically distinct.
Oelschlaegel
Uta
U
University Hospital, University of Technics, Medical Clinic and Policlinic I, Dresden, Germany. uta.oelschlaegel@uniklinikum-dresden.de
Mohr
Brigitte
B
Schaich
Markus
M
Schäkel
Ulrike
U
Kroschinsky
Frank
F
Illmer
Thomas
T
Ehninger
Gerhard
G
Thiede
Christian
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism; D001792:Blood Platelets / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D002871:Chromosome Banding; D004273:DNA, Neoplasm / Q000032:analysis; D005434:Flow Cytometry / Q000379:methods*; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007962:Leukocytes / Q000473:pathology; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D000090243:Nucleophosmin; D011446:Prospective Studies; D019718:Receptors, CXCR4 / Q000378:metabolism; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000378:metabolism
D018952:Antigens, CD34; C527276:CXCR4 protein, human; D004273:DNA, Neoplasm; D006684:HLA-DR Antigens; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D019718:Receptors, CXCR4; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3