Plasticity and Dynamics of Hematopoietic Cells within Bone Marrow Microenvironment in Leukemia

Extensive research has been conducted on the plasticity of malignant cells and nonmalignant cells in solid tumor. However, the plasticity of bone marrow hematopoietic cells in leukemia have remained largely unexplored. In this study, we aimed to investigate cell changings in hematopoietic cells through lineage tracing across various types of leukemias. We had compiled a landscape of leukemia and constructed phylogenetic trees of hematopoietic cells through utilizing massively parallel scRNA-seq data, mtDNA mutation and SNP analysis. Based on the observed cell changings, we identified several types of cell changings, including transdifferentiation, dedifferentiation, and state transition, except for differentiation and expansion. In AML and CMML, GMPs and neutrophils showed a higher potential for transferring to other cell types. In BPDCN, pDCs were less prone to switching to other cell types, while T cells demonstrated high plasticity. In B-ALL and B-CLL, B-ALL blast cells and B-CLL blast cells emerged at the most dynamic state. The dynamics of hematopoietic cells in AML, BPDCN and ALL changed along with the clinical process. Extrinsic factors within the leukemia microenvironment may influence the cell changings. Regulons encountered an intermediate cell state during the process of transition to myeloid cells and erythroid cells. We also found a correlation between B-common blast cells and T cells, suggesting a potential transition from B lymphoblastic leukemia to T lymphoblastic leukemia. In conclusion, our study unveiled the distinct plasticity and dynamics of hematopoietic cells in various types of leukemia. This sheds light on the possibility of targeting cell changes as a new strategy for leukemia treatment and improving current immunotherapy.