title: Immunophenotype of adult and childhood acute promyelocytic leukaemia: correlation with morphology, type of PML gene breakpoint and clinical outcome. A cooperative Italian study on 196 cases.
abstract: Acute promyelocytic leukaemia (APL), characterized by a specific PML-RARalpha fusion gene resulting from translocation t(15;17) and by a high response rate to differentiation therapy with all-trans retinoic acid, presents clinical (varying WBC counts, age and treatment outcome), morphological (hypergranular M3 and hypogranular M3V) and molecular (three isoforms of PML breakpoint) heterogeneity. We correlated leukaemic immunophenotype with these aspects in 196 molecularly confirmed APLs (63 children and 133 adults) in Italy. The bcr3 isoform (P = 0.05) and FAB M3V (P = 0.05) were more frequent in children. We confirmed in APL an immunophenotype characterized by frequent expression of CD13, CD33 and CD9 and rare expression of HLA-DR, CD10, CD7 and CD11b. However, we recognized CD2 in 28%, CD34 in 23% and CD19 in 11% of cases and demonstrated by double labelling that CD34 and CD2 may be co-expressed. CD2, CD34 and CD19 were significantly intercorrelated, and variably associated to other features: CD2 and CD34 with PML bcr3 (P < 0.001 and P < 0.001, respectively) and with M3V (P < 0.001 and P = 0.002), whereas only CD19 was directly correlated with WBC counts and only CD2 positively influenced CR rate (logistic model) and event-free survival (Cox model). We conclude that immunophenotype plays a role in the determination of the biological and clinical heterogeneity of childhood and adult APL.
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, Università degli Studi La Sapienza, Roma, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Guglielmi
authors.forename: M P
authors.initials: MP
authors.lastname: Martelli
authors.forename: D
authors.initials: D
authors.lastname: Diverio
authors.forename: S
authors.initials: S
authors.lastname: Fenu
authors.forename: M L
authors.initials: ML
authors.lastname: Vegna
authors.forename: A
authors.initials: A
authors.lastname: Cantù-Rajnoldi
authors.forename: A
authors.initials: A
authors.lastname: Biondi
authors.forename: M G
authors.initials: MG
authors.lastname: Cocito
authors.forename: L
authors.initials: L
authors.lastname: Del Vecchio
authors.forename: A
authors.initials: A
authors.lastname: Tabilio
authors.forename: G
authors.initials: G
authors.lastname: Avvisati
authors.forename: G
authors.initials: G
authors.lastname: Basso
authors.forename: F
authors.initials: F
authors.lastname: Lo Coco
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D018801:CD2 Antigens / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D015513:Oncogene Proteins / Q000032:analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051562:Proto-Oncogene Proteins c-bcr; D016896:Treatment Outcome
chemical_list: D015703:Antigens, CD; D018801:CD2 Antigens; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D011505:Protein-Tyrosine Kinases; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr