Prominin-1 (CD133) is essential for the determination of the phenotype of Philadelphia chromosome-positive leukemia

Metodieva, Anna, Karbanová, Jana, Chiriches, Claudia ORCID: https://orcid.org/0000-0003-3758-1892, Mian, Afsar Ali, Carmeliet, Peter, Tjwa, Marc, Corbeil, Denis and Ruthardt, Martin ORCID: https://orcid.org/0000-0003-1021-3811 2026. Prominin-1 (CD133) is essential for the determination of the phenotype of Philadelphia chromosome-positive leukemia. Experimental Hematology: Journal for Hematology, Stem Cell Biology and Transplantation , 105918. 10.1016/j.exphem.2026.105918

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Abstract

The human PROMININ-1 (PROM-1, CD133), detected by its AC133 epitope, is expressed on the surface of leukemia-initiating cells of Philadelphia chromosome-positive (Ph+) leukemia cells. Ninety-five percent of chronic myeloid leukemia (CML) cases are Ph+. Ph+ acute lymphoblastic leukemia (ALL) accounts for twenty-five to thirty percent of adult ALL and is considered a high-risk ALL subgroup. Targeting the t(9;22)-fusion protein BCR::ABL1 with ABL1-directed kinase inhibitors (TKIs) is a proven therapeutic concept for CML and Ph+ ALL. Resistance against TKI comprises mutations in BCR::ABL1, but many patients exhibit a primary resistance with unknown mechanisms. Here, we investigated the impact of PROM-1 on the leukemogenesis and the therapy response of Ph+ leukemias. We applied flow cytometry, co-immunoprecipitation, immunoblotting, stem cell assays, and leukemia induction in vivo to cell lines, syngeneic mouse models, and human Ph+ long-term cultures. We found a direct relationship between BCR::ABL1 and PROM-1, a shift from CML towards ALL upon the loss of Prom-1, as well as a link between the response to TKIs and the PROM-1 expression. In contrast to solid tumors, resistance was accompanied by a progressive loss of PROM-1. Our data suggest that PROM-1 plays an essential role in both cell fate decision and induction of the BCR::ABL1-related leukemic phenotype, highlighting its impact on the drug response of Ph+ leukemias.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine
Publisher:	Elsevier
ISSN:	0301-472X
Date of First Compliant Deposit:	13 October 2026
Date of Acceptance:	28 September 2026
Last Modified:	13 Oct 2026 09:45
URI:	https://orca.cardiff.ac.uk/id/eprint/190189

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