Intra‐heterogeneity in transcription and chemoresistant property of leukemia‐initiating cells in murine Setd2^−/− acute myeloid leukemia

Abstract

Background: Heterogeneity of leukemia-initiating cells (LICs) is a major obstacle in acute myeloid leukemia (AML) therapy. Accumulated evidence indicates that the coexistence of multiple types of LICs with different pathogenicity in the same individual is a common feature in AML. However, the functional heterogeneity including the drug response of coexistent LICs remains unclear. Therefore, this study aimed to clarify the intra-heterogeneity in LICs that can help predict leukemia behavior and develop more effective treatments.

Expression and Regulation Network of HDAC3 in Acute Myeloid Leukemia and the Implication for Targeted Therapy Based on Multidataset Data Mining

“…Acute myeloid leukemia has become the third leading cancer threat to human health today [24][25][26]. It is characterized by the rapid proliferation of abnormal cells in the bone marrow, which affects the production of normal hematopoietic cells.…”

Decoding leukemia at the single-cell level: clonal architecture, classification, microenvironment, and drug resistance

“… Showed that treatments combining DA and RAS pathway targeting may improve the clinical outcome of AML. [ 106 ] AML scRNA-seq Induced by chemotherapy, AML cells depleted LSCs and entered a senescent-like phenotype. This kind of senescence was transient with increased engraftment ability.…”

“…( 6 ) Mac-1 was found to be differentially expressed in LSCs. Mac-1 + subtype is DA resistant with higher RAS pathway activation [ 106 ] …”

“…Applying scRNA-seq, another study identified two subsets of LSCs featured by c-Kit + B220 + Mac-1 − and c-Kit + B220 + Mac-1 + , respectively (Fig. 6 ) [ 106 ]. The c-Kit + B220 + Mac-1 + cells displayed intrinsic resistance when subjected to the DA treatment in vivo, with the higher activation of the RAS pathway.…”

“…The c-Kit + B220 + Mac-1 + cells displayed intrinsic resistance when subjected to the DA treatment in vivo, with the higher activation of the RAS pathway. Thus, the combination therapy involving DA and RAS inhibitors effectively impeded disease progression in the murine model [ 106 ].…”