title: Distribution and levels of cell surface expression of CD33 and CD123 in acute myeloid leukemia.
abstract: Owing to the more recent positive results with the anti-CD33 immunotoxin gemtuzumab ozogamicin, therapy against acute myeloid leukemias (AMLs) targeting CD33 holds many promises. Here, CD33 and CD123 expression on AML blasts was studied by flow cytometry in a cohort of 319 patients with detailed information on French-American-British/World Health Organization (FAB/WHO) classification, cytogenetics and molecular aberrations. AMLs of 87.8% express CD33 and would therefore be targetable with anti-CD33 therapies. Additionally, 9.4% of AMLs express CD123 without concomitant CD33 expression. Thus, nearly all AMLs could be either targeted via CD33 or CD123. Simultaneous presence of both antigens was observed in 69.5% of patients. Most importantly, even AMLs with adverse cytogenetics express CD33 and CD123 levels comparable to those with favorable and intermediate subtypes. Some patient groups with unfavorable alterations, such as FMS-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations, high FLT3-ITD mutant/wild-type ratios and monosomy 5 are even characterized by high expression of CD33 and CD123. In addition, blasts of patients with mutant nucleophosmin (NPM1) revealed significantly higher CD33 and CD123 expression pointing toward the possibility of minimal residual disease-guided interventions in mutated NPM1-positive AMLs. These results stimulate the development of novel concepts to redirect immune effector cells toward CD33- and CD123-expressing blasts using bi-specific antibodies or engineered T cells expressing chimeric antigen receptors.
authors.affiliation: Medizinische Klinik und Poliklinik I, University Hospital 'Carl Gustav Carus', Technische Universität Dresden, Dresden, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Ehninger
authors.affiliation: Medizinische Klinik und Poliklinik I, University Hospital 'Carl Gustav Carus', Technische Universität Dresden, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kramer
authors.affiliation: Medizinische Klinik und Poliklinik I, University Hospital 'Carl Gustav Carus', Technische Universität Dresden, Dresden, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Röllig
authors.affiliation: Medizinische Klinik und Poliklinik I, University Hospital 'Carl Gustav Carus', Technische Universität Dresden, Dresden, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Thiede
authors.affiliation: Medizinische Klinik und Poliklinik I, University Hospital 'Carl Gustav Carus', Technische Universität Dresden, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bornhäuser
authors.affiliation: Medizinische Klinik und Poliklinik I, University Hospital 'Carl Gustav Carus', Technische Universität Dresden, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: von Bonin
authors.affiliation: Medizinische Klinik und Poliklinik I, University Hospital 'Carl Gustav Carus', Technische Universität Dresden, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Wermke
authors.affiliation: Institute of Immunology, Medical Faculty 'Carl Gustav Carus', Technische Universität Dresden, Dresden, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Feldmann
authors.affiliation: Institute of Immunology, Medical Faculty 'Carl Gustav Carus', Technische Universität Dresden, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bachmann
authors.affiliation: Medizinische Klinik und Poliklinik I, University Hospital 'Carl Gustav Carus', Technische Universität Dresden, Dresden, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Ehninger
authors.affiliation: Medizinische Klinik und Poliklinik I, University Hospital 'Carl Gustav Carus', Technische Universität Dresden, Dresden, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Oelschlägel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053650:Interleukin-3 Receptor alpha Subunit / Q000096:biosynthesis*; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D000090243:Nucleophosmin; D012307:Risk Factors; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000096:biosynthesis*; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000097:blood / Q000235:genetics
chemical_list: C571163:CD33 protein, human; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit; C000716967:NPM1 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3