title: High levels of CD34+CD38low/-CD123+ blasts are predictive of an adverse outcome in acute myeloid leukemia: a Groupe Ouest-Est des Leucemies Aigues et Maladies du Sang (GOELAMS) study.
abstract: BACKGROUND
  Acute myeloid leukemias arise from a rare population of leukemic cells, known as leukemic stem cells, which initiate the disease and contribute to frequent relapses. Although the phenotype of these cells remains unclear in most patients, these cells are enriched within the CD34(+)CD38(low/-) compartment expressing the interleukin-3 alpha chain receptor, CD123. The aim of this study was to determine the prognostic value of the percentage of blasts with the CD34(+)CD38(low/-)CD123(+) phenotype.
  
  
  METHODS
  The percentage of CD34(+)CD38(low/-)CD123(+) cells in the blast population was determined at diagnosis using flow cytometry. One hundred and eleven patients under 65 years of age with de novo acute myeloid leukemia and treated with intensive chemotherapy were retrospectively included in the study. Correlations with complete response, disease-free survival and overall survival were evaluated with univariate and multivariate analyses.
  
  
  RESULTS
  A proportion of CD34(+)CD38(low/-)CD123(+) cells greater than 15% at diagnosis and an unfavorable karyotype were significantly correlated with a lack of complete response. By logistic regression analysis, a percentage of CD34(+)CD38(low/-)CD123(+) higher than 15% retained significance with an odds ratio of 0.33 (0.1-0.97; P=0.044). A greater than 1% population of CD34(+)CD38(low/-)CD123(+) cells negatively affected disease-free survival (0.9 versus 4.7 years; P<0.0001) and overall survival (1.25 years versus median not reached; P<0.0001). A greater than 1% population of CD34(+)CD38(low/-)CD123(+) cells retained prognostic significance for both parameters after multivariate analysis.
  
  
  CONCLUSIONS
  The percentage of CD34(+)CD38(low/-)CD123(+) leukemic cells at diagnosis was significantly correlated with response to treatment and survival. This prognostic marker might be easily adopted in clinical practice to rapidly identify patients at risk of treatment failure.
authors.affiliation: Institut Cochin, Immuno-hematology Department, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Vergez
authors.forename: Alexa S
authors.initials: AS
authors.lastname: Green
authors.forename: Jerome
authors.initials: J
authors.lastname: Tamburini
authors.forename: Jean-Emmanuel
authors.initials: JE
authors.lastname: Sarry
authors.forename: Baptiste
authors.initials: B
authors.lastname: Gaillard
authors.forename: Pascale
authors.initials: P
authors.lastname: Cornillet-Lefebvre
authors.forename: Melanie
authors.initials: M
authors.lastname: Pannetier
authors.forename: Aymeric
authors.initials: A
authors.lastname: Neyret
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chapuis
authors.forename: Norbert
authors.initials: N
authors.lastname: Ifrah
authors.forename: François
authors.initials: F
authors.lastname: Dreyfus
authors.forename: Stéphane
authors.initials: S
authors.lastname: Manenti
authors.forename: Cecile
authors.initials: C
authors.lastname: Demur
authors.forename: Eric
authors.initials: E
authors.lastname: Delabesse
authors.forename: Catherine
authors.initials: C
authors.lastname: Lacombe
authors.forename: Patrick
authors.initials: P
authors.lastname: Mayeux
authors.forename: Didier
authors.initials: D
authors.lastname: Bouscary
authors.forename: Christian
authors.initials: C
authors.lastname: Recher
authors.forename: Valerie
authors.initials: V
authors.lastname: Bardet
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000097:blood*; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000097:blood*; D000951:Antigens, Neoplasm / Q000097:blood*; D001752:Blast Crisis / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D005260:Female; D006801:Humans; D053650:Interleukin-3 Receptor alpha Subunit / Q000097:blood*; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D007958:Leukocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D011379:Prognosis
chemical_list: D018952:Antigens, CD34; D000951:Antigens, Neoplasm; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit; D008562:Membrane Glycoproteins; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1