Research on PD-1 as a Stem Cell Marker for Blast Phase of Chronic Myeloid Leukemia

The purpose of this study was to investigate the role of Programmed Death-1 (PD-1) as a stem cell marker in the blast phase of chronic myeloid leukemia (BP-CML). We used a mouse model of BP-CML, induced by infecting bone marrow cells with P210-BCR-ABL1-NGFR and Nup98/HoxA9 retroviruses. Flow cytometry was employed to analyze the expression of PD-1 and Tim-3 immune checkpoints on the surface of spleen cells from BP-CML mice and to determine the proportion of PD-1 positive cells within the leukemia stem cell compartment. PD-1 positive (PD-1+) and PD-1 negative (PD-1–) BP-CML cells were sorted by flow cytometry and then infused into recipient mice to assess their pathogenic potential. Our results revealed that the spleen volumes of BP-CML mice were significantly increased compared to those of wild-type mice. Additionally, BP-CML cells exhibited high expression of PD-1 molecules, and PD-1+ BP-CML cells showed elevated expression of hematopoietic stem cell markers (C-KIT+SCA-1+) and the acute myeloid leukemia stem cell marker (Tim-3). Mice infused with PD-1+ cells had a significantly shorter survival time compared to those infused with PD-1– cells. Furthermore, analysis of the GEO and TCGA databases indicated that PD-1 expression was inversely correlated with the prognosis of leukemia patients. These findings suggest that PD-1 may serve as a novel stem cell marker for BP-CML and could potentially contribute to the progression of leukemia.