Characterization of bone marrow heterogeneity in NK-AML (M4/M5) based on single-cell RNA sequencing

Wu, Wenqi; Shi, Zhanying; Tang, Zhongyuan; Li, Huiqun; Huang, Xiaoke; Liang, Xiaolin; Li, Jing; Yao, Yibin; Zhao, Weihua; Wu, Meiqing; Luo, Jun; Liu, Zhenfang

doi:10.1186/s40164-023-00391-5

Cited by 5 publications

(4 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, CD96, a known LSC marker mentioned earlier, was upregulated in only one patient, suggesting that LSC might be patient-specific too. In normal karyotype AML (FAB AML-M4/5), a presumable LSC cluster highly expressing CD34 , CD38 , CD96 , CD46 , CD47 , CD82, CD44 and CD133 was uncovered ( Figure 2E ) ( 40 ). However, due to the small sample size in these two studies ( 40 , 59 ), further validation of these findings in a larger cohort of AML patients is necessary to determine their general applicability.…”

Section: Characterizing Leukemia Stem Cellsmentioning

confidence: 99%

“…In normal karyotype AML (FAB AML-M4/5), a presumable LSC cluster highly expressing CD34 , CD38 , CD96 , CD46 , CD47 , CD82, CD44 and CD133 was uncovered ( Figure 2E ) ( 40 ). However, due to the small sample size in these two studies ( 40 , 59 ), further validation of these findings in a larger cohort of AML patients is necessary to determine their general applicability. In NPM1 mut AML, scRNA-seq provided a higher resolution and further anatomized the miR-126 high LSCs into dormant and cycling sub-compartment.…”

Section: Characterizing Leukemia Stem Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Unveiling novel insights in acute myeloid leukemia through single-cell RNA sequencing

Zhou,

Chng

2024

Front. Oncol.

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is a complex and heterogeneous group of aggressive hematopoietic stem cell disease. The presence of diverse and functionally distinct populations of leukemia cells within the same patient’s bone marrow or blood poses a significant challenge in diagnosing and treating AML. A substantial proportion of AML patients demonstrate resistance to induction chemotherapy and a grim prognosis upon relapse. The rapid advance in next generation sequencing technologies, such as single-cell RNA-sequencing (scRNA-seq), has revolutionized our understanding of AML pathogenesis by enabling high-resolution interrogation of the cellular heterogeneity in the AML ecosystem, and their transcriptional signatures at a single-cell level. New studies have successfully characterized the inextricably intertwined interactions among AML cells, immune cells and bone marrow microenvironment and their contributions to the AML development, therapeutic resistance and relapse. These findings have deepened and broadened our understanding the complexity and heterogeneity of AML, which are difficult to detect with bulk RNA-seq. This review encapsulates the burgeoning body of knowledge generated through scRNA-seq, providing the novel insights and discoveries it has unveiled in AML biology. Furthermore, we discuss the potential implications of scRNA-seq in therapeutic opportunities, focusing on immunotherapy. Finally, we highlight the current limitations and future direction of scRNA-seq in the field.

show abstract

Section: Characterizing Leukemia Stem Cellsmentioning

confidence: 99%

Section: Characterizing Leukemia Stem Cellsmentioning

confidence: 99%

Unveiling novel insights in acute myeloid leukemia through single-cell RNA sequencing

Zhou,

Chng

2024

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…Some progenitor AML cells proliferated and differentiated with an expression of OXPHOS expression signature, while others were OXPHOS (low) miR-126 (high) and displayed high stemness and quiescence features [ 127 ] 2023 Human 10 × Genomics Correspondence with authors Identified a distinct LSC-like cluster with possible biomarkers in NK-AML (M4/M5). Provided an atlas of NK-AML (M4/M5) cell heterogeneity, composition, and biomarkers with implications for precision medicine and targeted therapies [ 262 ] 2023 Human 10 × Genomics GSE213584 Identified unique C1Q + macrophage-like leukemia cells. C1Q was identified as a marker for AML with adverse prognosis, orchestrated cancer infiltration pathway activity by communication with fibroblasts, and represents a compelling therapeutic target for EMI [ 263 ] Acute lymphoblastic leukemia 2020 Human 10 × Genomics GSE134759 Monocyte abundance was predictive of pediatric and adult B-ALL patient survival.…”

Section: Clinical Applications Of Scrna-seq In Leukemiamentioning

confidence: 99%

Advances in single-cell RNA sequencing and its applications in cancer research

Huang,

Ma,

et al. 2023

J Hematol Oncol

View full text Add to dashboard Cite

Cancers are a group of heterogeneous diseases characterized by the acquisition of functional capabilities during the transition from a normal to a neoplastic state. Powerful experimental and computational tools can be applied to elucidate the mechanisms of occurrence, progression, metastasis, and drug resistance; however, challenges remain. Bulk RNA sequencing techniques only reflect the average gene expression in a sample, making it difficult to understand tumor heterogeneity and the tumor microenvironment. The emergence and development of single-cell RNA sequencing (scRNA-seq) technologies have provided opportunities to understand subtle changes in tumor biology by identifying distinct cell subpopulations, dissecting the tumor microenvironment, and characterizing cellular genomic mutations. Recently, scRNA-seq technology has been increasingly used in cancer studies to explore tumor heterogeneity and the tumor microenvironment, which has increased the understanding of tumorigenesis and evolution. This review summarizes the basic processes and development of scRNA-seq technologies and their increasing applications in cancer research and clinical practice.

show abstract

“…Acute myeloid leukemia (AML) is a highly heterogeneous disease characterized by complex cytogenetic and molecular landscape, leading to diverse prognostic outcomes [ 1 , 2 ]. The t(8;21)(q22;q22) chromosomal translocation is one of the most common cytogenetic abnormalities in AML [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

A novel AML1-ETO/FTO positive feedback loop promotes leukemogenesis and Ara-C resistance via stabilizing IGFBP2 in t(8;21) acute myeloid leukemia

Zhou,

Li,

Wang

et al. 2024

Exp Hematol Oncol

View full text Add to dashboard Cite

Background t(8;21)(q22;q22) is one of the most frequent chromosomal abnormalities in acute myeloid leukemia (AML), leading to the generation of the fusion protein AML1-ETO. Despite t(8;21) AML being considered as a subtype with a favorable prognosis, approximately 30–50% of patients experience drug resistance and subsequent relapse. N6-methyladenosine (m6A) is demonstrated to be involved in the development of AML. However, the regulatory mechanisms between AML1-ETO and m6A-related enzymes and the roles of dysregulated m6A modifications in the t(8;21)-leukemogenesis and chemoresistance remain elusive. Methods Chromatin immunoprecipitation, dual-luciferase reporter assay, m6A-qPCR, RNA immunoprecipitation, and RNA stability assay were used to investigate a regulatory loop between AML1-ETO and FTO, an m6A demethylase. Gain- and loss-of-function experiments both in vitro and in vivo were further performed. Transcriptome-wide RNA sequencing and m6A sequencing were conducted to identify the potential targets of FTO. Results Here we show that FTO is highly expressed in t(8;21) AML, especially in patients with primary refractory disease. The expression of FTO is positively correlated with AML1-ETO, which is attributed to a positive regulatory loop between the AML1-ETO and FTO. Mechanistically, AML1-ETO upregulates FTO expression through inhibiting the transcriptional repression of FTO mediated by PU.1. Meanwhile, FTO promotes the expression of AML1-ETO by inhibiting YTHDF2-mediated AML1-ETO mRNA decay. Inactivation of FTO significantly suppresses cell proliferation, promotes cell differentiation and renders resistant t(8;21) AML cells sensitive to Ara-C. FTO exerts functions by regulating its mRNA targets, especially IGFBP2, in an m6A-dependent manner. Regain of Ara-C tolerance is observed when IGFBP2 is overexpressed in FTO-knockdown t(8;21) AML cells. Conclusion Our work reveals a therapeutic potential of targeting AML1-ETO/FTO/IGFBP2 minicircuitry in the treatment for t(8;21) patients with resistance to Ara-C.

show abstract

Characterization of bone marrow heterogeneity in NK-AML (M4/M5) based on single-cell RNA sequencing

Cited by 5 publications

References 42 publications

Unveiling novel insights in acute myeloid leukemia through single-cell RNA sequencing

Unveiling novel insights in acute myeloid leukemia through single-cell RNA sequencing

Advances in single-cell RNA sequencing and its applications in cancer research

A novel AML1-ETO/FTO positive feedback loop promotes leukemogenesis and Ara-C resistance via stabilizing IGFBP2 in t(8;21) acute myeloid leukemia

Contact Info

Product

Resources

About