title: Negative prognostic value of CD34 antigen also if expressed on a small population of acute promyelocytic leukemia cells.
abstract: Potential clinical significance of CD34 expression in acute promyelocitic leukemia (APL) has not been deeply investigated. We hereby analyzed the clinico-biological features and treatment outcome of APL patients in relation to CD34 expression, even when expressed in a small subpopulation: 114 APL patients homogeneously treated with the AIDA schedule were included in the study and prognostic correlation with respect to CD34 expression, both when expressed in association with CD2 and as isolated expression (cutoff ≥2 to <10 % or ≥10 %), were investigated. CD34 was associated to CD2 in 30 patients and was isolated in 19 patients. When compared to the CD34-negative population, CD34/CD2 expression identified a subgroup with characteristic features: M3 variant subtype (26 vs 7 % in the negative group, p = 0.02), bcr3 transcript subtype (73 vs 32 %, p = 0.001), high risk according to the risk of relapse (66 vs 17 %, p = 0.002), high incidence of differentiation syndrome (26 vs 12 %, p = 0.01), lower overall survival (88 vs 95 %), and a significantly higher rate of relapse (22 vs 13.8 %, p = 0.05). We then evaluated the prognostic value of isolated CD34 expression: it was detected in nine patients with a cutoff of expression ≥10 % and in 10 patients with a cutoff ≥2 but <10 %. Isolated CD34 positivity identified a subgroup with a classic morphology (79 %), bcr1 prevalence (53 %), higher rate of relapse (37 vs 13.8 % in the negative group, p = 0.002), higher incidence of differentiation syndrome (55 vs 12 %, p = 0.03), and lower overall survival (60 vs 95 %, p = 0.001). The results of our study confirm that CD34/CD2 expression characterizes a subset of APL with a high WBC count and a variant morphological subtype, associated with an unfavorable clinical course. We also show that the isolated expression of CD34, even at a low cutoff, identifies a group of classic APL with a negative prognosis. Further studies aimed at identifying other molecular signatures in CD34-positive patients are needed in order to optimize the therapeutic strategy for this subset of patients.
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University, Via Benevento 6, 00161, Rome, Italy, breccia@bce.uniroma1.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Breccia
authors.forename: Maria Stefania
authors.initials: MS
authors.lastname: De Propris
authors.forename: Caterina
authors.initials: C
authors.lastname: Stefanizzi
authors.forename: Sara
authors.initials: S
authors.lastname: Raponi
authors.forename: Matteo
authors.initials: M
authors.lastname: Molica
authors.forename: Gioia
authors.initials: G
authors.lastname: Colafigli
authors.forename: Clara
authors.initials: C
authors.lastname: Minotti
authors.forename: Roberto
authors.initials: R
authors.lastname: Latagliata
authors.forename: Daniela
authors.initials: D
authors.lastname: Diverio
authors.forename: Anna
authors.initials: A
authors.lastname: Guarini
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D007958:Leukocyte Count / Q000379:methods; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods
chemical_list: D018952:Antigens, CD34