The role of the primitive marker CD133 in CD34-negative acute myeloid leukemia for the detection of leukemia stem cells

Tom Reuvekamp; Luca L G Janssen; Lok Lam Ngai; Jannemieke Carbaat-Ham; Daphne den Hartog; Willemijn J Scholten; Angèle Kelder; Diana Hanekamp; Eliza Wensink; Noortje van Gils; Patrycja Gradowska; Bob Löwenberg; Gert J Ossenkoppele; Arjan A van de Loosdrecht; Theresia M Westers; Linda Smit; Costa Bachas; Jacqueline Cloos

doi:10.1002/cyto.b.22201

The role of the primitive marker CD133 in CD34-negative acute myeloid leukemia for the detection of leukemia stem cells

Cytometry B Clin Cytom. 2024 Aug 23. doi: 10.1002/cyto.b.22201. Online ahead of print.

Authors

Tom Reuvekamp^{1

2

3}, Luca L G Janssen^{1

2}, Lok Lam Ngai^{1

2}, Jannemieke Carbaat-Ham^{1

2}, Daphne den Hartog^{1

2}, Willemijn J Scholten^{1

2}, Angèle Kelder^{1

2}, Diana Hanekamp^{1

2

4}, Eliza Wensink⁵, Noortje van Gils^{1

2}, Patrycja Gradowska^{4

6}, Bob Löwenberg⁴, Gert J Ossenkoppele^{1

2}, Arjan A van de Loosdrecht^{1

2}, Theresia M Westers^{1

2}, Linda Smit^{1

2}, Costa Bachas^{1

2}, Jacqueline Cloos^{1

2}

Affiliations

¹ Department of Hematology, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
² Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands.
³ Department of Hematology, Amsterdam UMC location Universiteit van Amsterdam, Amsterdam, The Netherlands.
⁴ Department of Hematology, Erasmus MC Cancer Institute and University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁵ Department of Radiology and Nuclear Medicine, Amsterdam UMC location Universiteit van Amsterdam, Amsterdam, The Netherlands.
⁶ HOVON Foundation, Rotterdam, The Netherlands.

PMID: 39177948
DOI: 10.1002/cyto.b.22201

Abstract

The most important reason for dismal outcomes in acute myeloid leukemia (AML) is the development of relapse. Leukemia stem cells (LSCs) are hypothesized to initiate relapse, and high CD34+CD38- LSC load is associated with poor prognosis. In 10% of AML patients, CD34 is not or is low expressed on the leukemic cells (<1%), and CD34+CD38- LSCs are absent. These patients are classified as CD34-negative. We aimed to determine whether the primitive marker CD133 can detect LSCs in CD34-negative AML. We retrospectively quantified 148 CD34-negative patients for proportions of CD34-CD133+ and CD133+CD38- cell fractions in the diagnostic samples of CD34-negative patients in the HOVON102 and HOVON132 trials. No prognostic difference was found between patients with high or low proportions of CD34-CD133+, which is found to be aberrantly expressed in AML. A high level of CD133+CD38- cells was not associated with poor overall survival, and expression in AML was similar to normal bone marrow. To conclude, CD133 is useful as an additional primitive marker for the detection of leukemic blast cells in CD34-negative AML. However, CD133+CD38 alone is not suitable for the detection of LSCs at diagnosis.

Keywords: CD133; acute myeloid leukemia; flow cytometry; leukemia stem cells; measurable residual disease.