BACKGROUND: CD33 (Siglec-3) is becoming increasingly important as a target of antibody-mediated therapy in acute myeloid leukaemia (AML). In normal myelopoiesis, expression of CD33 is restricted to advanced stages of differentiation, whereas primitive stem cells do not express CD33. In the present study, we asked whether leukaemic stem cells in patients with AML express CD33. MATERIALS AND METHODS: A multicolour-staining technique was applied in 11 patients with AML, and leukaemic progenitors defined as CD34(+)/CD38(-)/CD123(+) cells. AML stem cells were purified by cell sorting and were examined for expression of CD33 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: In all patients in whom the majority of myeloblasts expressed CD33 (n = 8), AML progenitors reacted with the CD33 antibody P67.6. Repopulation experiments utilizing irradiated NOD/SCID mice confirmed that AML stem cells in these patients reside within the CD33(+) subpopulation of the leukaemic clone. Moreover, highly purified AML stem cells (> 98% purity) from patients with CD33(+) AML were found to express CD33 mRNA in RT-PCR analyses. CD33 was neither detectable on CD34(+)/CD38(-) cells in normal bone marrow nor on leukaemic stem cells in patients with CD33-negative AML. CONCLUSIONS: Leukaemic stem cells in patients with CD33(+) AML express CD33. This observation is in favour of novel treatment concepts employing CD33-targeting antibodies in AML.
BACKGROUND:CD33 (Siglec-3) is becoming increasingly important as a target of antibody-mediated therapy in acute myeloid leukaemia (AML). In normal myelopoiesis, expression of CD33 is restricted to advanced stages of differentiation, whereas primitive stem cells do not express CD33. In the present study, we asked whether leukaemic stem cells in patients with AML express CD33. MATERIALS AND METHODS: A multicolour-staining technique was applied in 11 patients with AML, and leukaemic progenitors defined as CD34(+)/CD38(-)/CD123(+) cells. AML stem cells were purified by cell sorting and were examined for expression of CD33 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: In all patients in whom the majority of myeloblasts expressed CD33 (n = 8), AML progenitors reacted with the CD33 antibody P67.6. Repopulation experiments utilizing irradiated NOD/SCIDmice confirmed that AML stem cells in these patients reside within the CD33(+) subpopulation of the leukaemic clone. Moreover, highly purified AML stem cells (> 98% purity) from patients with CD33(+) AML were found to express CD33 mRNA in RT-PCR analyses. CD33 was neither detectable on CD34(+)/CD38(-) cells in normal bone marrow nor on leukaemic stem cells in patients with CD33-negative AML. CONCLUSIONS: Leukaemic stem cells in patients with CD33(+) AML express CD33. This observation is in favour of novel treatment concepts employing CD33-targeting antibodies in AML.
Authors: Heidrun Karlic; Harald Herrmann; Axel Schulenburg; Thomas W Grunt; Sylvia Laffer; Irina Mirkina; Rainer Hubmann; Medhat Shehata; Brigitte Marian; Edgar Selzer; Michael Pfeilstöcker; Elisabeth Pittermann; Ulrich Jäger; Hubert Pehamberger; Christoph Zielinski; Peter Valent Journal: Wien Klin Wochenschr Date: 2010-07-22 Impact factor: 1.704
Authors: Sargur Madabushi Srideshikan; Jamison Brooks; Darren Zuro; Bijender Kumar; James Sanchez; Liliana Echavarria Parra; Marvin Orellana; Paresh Vishwasrao; Indu Nair; Junie Chea; Kofi Poku; Nicole Bowles; Aaron Miller; Todd Ebner; Justin Molnar; Joseph Rosenthal; Daniel A Vallera; Jeffrey Y C Wong; Anthony S Stein; David Colcher; John E Shively; Paul J Yazaki; Susanta K Hui Journal: Clin Cancer Res Date: 2019-09-23 Impact factor: 12.531
Authors: Mohamed Rahmani; Jewel Nkwocha; Elisa Hawkins; Xinyan Pei; Rebecca E Parker; Maciej Kmieciak; Joel D Leverson; Deepak Sampath; Andrea Ferreira-Gonzalez; Steven Grant Journal: Cancer Res Date: 2018-03-20 Impact factor: 12.701
Authors: Harald Herrmann; Irina Sadovnik; Gregor Eisenwort; Thomas Rülicke; Katharina Blatt; Susanne Herndlhofer; Michael Willmann; Gabriele Stefanzl; Sigrid Baumgartner; Georg Greiner; Axel Schulenburg; Niklas Mueller; Werner Rabitsch; Martin Bilban; Gregor Hoermann; Berthold Streubel; Daniel A Vallera; Wolfgang R Sperr; Peter Valent Journal: Blood Adv Date: 2020-10-27