Details

Autor(en) / Beteiligte

• Ehninger, A
• Kramer, M
• Röllig, C
• Thiede, C
• Bornhäuser, M
• von Bonin, M
• Wermke, M
• Feldmann, A
• Bachmann, M
• Ehninger, G
• Oelschlägel, U

Titel

Distribution and levels of cell surface expression of CD33 and CD123 in acute myeloid leukemia

Ist Teil von

• Blood cancer journal (New York), 2014-06, Vol.4 (6), p.e218-e218

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2014

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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.