Single-cell mapping portrays the distinct expression features between chronic phase and B-lymphoblastic crisis samples from patients with CML

ABSTRACT: Background: Chronic myeloid leukemia (CML) is a biphasic clonal hematopoietic stem cell disorder driven by the Philadelphia chromosome (Ph)-encoded BCR::ABL1 oncogene. The blast phase (BP) in CML progressed from indolent chronic phase (CP), usually has a dismal outcome. Single-cell RNA sequencing (scRNA-seq) have identified the pretreatment features linked to therapy resistance and disease progression. However, data on CML in B-cell lymphoblastic crisis (BLBC) remain limited. Methods: We performed the scRNA-seq on bone marrow cells derived from paired CML-CP and CML-BLBC samples to evaluate their underlying cellular heterogeneity. and. Additionally, we also unveil the distinct gene expression signatures of BLBC samples by comparing with CP samples and de novo Ph-positive (Ph+) B-cell acute lymphoblastic leukemia (B-ALL) samples. Results: By constructing a single-cell atlas, we delineated that the hematopoietic lineage of different patients skewed towards to erythroid or myeloid progenitors at their CP diagnosis respectively, which was consistent with the enrichment of gene sets related to canonical erythroid regulator GATA1 and myeloid regulator EVI1. Patient-specific B-cell progenitor types including PreB, ProB, and ImmatureB cells further illustrated the clear inter-tumor heterogeneity within CML-BLBC samples. Comparative analysis revealed that CP cells presented strong proliferation and oxidative phosphorylation characteristics, and BLBC cell populations had a series of unique expression features encompassing elevated stemness and relative quiescence, enhanced inflammatory (interferon gamma [IFN-γ], IFN-α, IL12, and IL6) and apoptotic signaling pathways, as well as ed previously unreported augmentation in ERBB2 and epithelial to mesenchymal transition (EMT) pathways. In single-cell data of CML-BLBC, we also confirmed a remarkably increased expression of DNTT which has been shown to predict BLBC transformation at diagnosis. Importantly, CD24 displayed a striking upregulation in CML-BLBC samples when compared with both the CML-CP and Ph+ B-ALL samples, suggesting the potential as a target in the future therapy of patients with CML-BLBC. Conclusion: In summary, our study presents a single-cell atlas which portrays the cellular heterogeneity and distinct cell state of CML-CP and CML-BLBC samples, as well as abnormal high expression of CD24 in patients with CML-BLBC. These findings may imply unique functional behaviors and therapeutic vulnerabilities of CML-BLBC, and thereby facilitating the development of detection methods, further enabling the identification of high-risk CP patients at diagnosis, and preventing the progression to BP through further early intervention.

ORGANISM(S): Homo sapiens

PROVIDER: GSE333588 | GEO | 2026/06/02

REPOSITORIES: GEO