Integrated single-cell transcriptome analysis of CD34 + enriched leukemic stem cells revealed intra- and inter-patient transcriptional heterogeneity in pediatric acute myeloid leukemia

Thakral, Deepshi; Singh, Vivek Kumar; Gupta, Ritu; Jha, Nitu; Khan, Aafreen; Kaur, Gurvinder; Rai, Sandeep; Kumar, Vijay; Supriya, Manisha; Bakhshi, Sameer; Seth, Rachna

doi:10.1007/s00277-022-05021-4

Cited by 7 publications

(3 citation statements)

References 49 publications

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“…LCs are disease-specific cells that originate from progenitor cells. Studies comparing HSCs and LCs have been conducted previously to identify LC characteristics and find treatment targets ( Eppert et al, 2011 ; Sachs et al, 2020 ; Schuurhuis et al, 2013 ; Thakral et al, 2023 ). We also aimed to identify differences in the transcriptome between HSCs and LCs.…”

Section: Resultsmentioning

confidence: 99%

Identification of Cell Type-Specific Effects of DNMT3A Mutations on Relapse in Acute Myeloid Leukemia

Bae,

Kim,

Kim

et al. 2023

Molecules and Cells

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Section: Resultsmentioning

confidence: 99%

Identification of Cell Type-Specific Effects of DNMT3A Mutations on Relapse in Acute Myeloid Leukemia

Bae,

Kim,

Kim

et al. 2023

Molecules and Cells

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“…The BCL file generated was converted to fastq using bcl2fastq (v2.20), raw reads were subjected for further processing through the BD Rhapsody Whole‐Transcriptome Assay Analysis Pipeline (https://www.sevenbridges.com/). The data were analysed using Seurat and principal component analysis, as described previously 21 …”

Section: Methodsmentioning

confidence: 99%

Immunophenotypic characterization of leukemic stem cells in acute myeloid leukemia using single tube 10‐colour panel by multiparametric flow cytometry: Deciphering the spectrum, complexity and immunophenotypic heterogeneity

Das,

Panda,

Gajendra

et al. 2024

Int J Lab Hematology

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IntroductionDespite extensive research, comprehensive characterization of leukaemic stem cells (LSC) and information on their immunophenotypic differences from normal haematopoietic stem cells (HSC) is lacking. Herein, we attempted to unravel the immunophenotypic (IPT) characteristics and heterogeneity of LSC using multiparametric flow cytometry (MFC) and single‐cell sequencing.Materials and MethodsBone marrow aspirate samples from patients with acute myeloid leukaemia (AML) were evaluated using MFC at diagnostic and post induction time points using a single tube‐10‐colour‐panel containing LSC‐associated antibodies CD123, CD45RA, CD44, CD33 and COMPOSITE (CLL‐1, TIM‐3, CD25, CD11b, CD22, CD7, CD56) with backbone markers that is, CD45, CD34, CD38, CD117, sCD3. Single‐cell sequencing of the whole transcriptome was also done in a bone marrow sample.ResultsLSCs and HSCs were identified in 225/255 (88.2%) and 183/255 (71.6%) samples, respectively. Significantly higher expression was noted for COMPOSITE, CD45RA, CD123, CD33, and CD44 in LSCs than HSCs (p < 0.0001). On comparing the LSC specific antigen expressions between CD34+ (n = 184) and CD34‐ LSCs (n = 41), no difference was observed between the groups. More than one sub‐population of LSC was demonstrated in 4.4% of cases, which further revealed high concordance between MFC and single cell transcriptomic analysis in one of the cases displaying three LSC subpopulations by both methods.ConclusionA single tube‐10‐colour MFC panel is proposed as an easy and reproducible tool to identify and discriminate LSCs from HSCs. LSCs display both inter‐ and intra‐sample heterogeneity in terms of antigen expressions, which opens the facets for single cell molecular analysis to elucidate the role of subpopulations of LSCs in AML progression.

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“…Much of what has been published about pediatric AML stem cell biology borrows heavily from certain foundational tenets of adult AML stem cells, which can at times create limitations in the data. For example, many of the pediatric LSC studies base their investigation of pediatric LSCs on CD34+CD38-sorted populations of cells, which in most cases is enriching for LSCs in the context of adult AML but may miss the LSC heterogeneity that we now know is present [57][58][59][60][61][62]. With those caveats in mind, the findings from these studies could still prove to be therapeutically and prognostically interesting.…”

Section: Lsc Biology In Pediatric Myeloid Diseasementioning

confidence: 99%

Emerging and Future Targeted Therapies for Pediatric Acute Myeloid Leukemia: Targeting the Leukemia Stem Cells

Murphy,

Winters

2023

Biomedicines

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Acute myeloid leukemia (AML) is a rare subtype of acute leukemia in the pediatric and adolescent population but causes disproportionate morbidity and mortality in this age group. Standard chemotherapeutic regimens for AML have changed very little in the past 3–4 decades, but the addition of targeted agents in recent years has led to improved survival in select subsets of patients as well as a better biological understanding of the disease. Currently, one key paradigm of bench-to-bedside practice in the context of adult AML is the focus on leukemia stem cell (LSC)-targeted therapies. Here, we review current and emerging immunotherapies and other targeted agents that are in clinical use for pediatric AML through the lens of what is known (and not known) about their LSC-targeting capability. Based on a growing understanding of pediatric LSC biology, we also briefly discuss potential future agents on the horizon.

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Integrated single-cell transcriptome analysis of CD34 + enriched leukemic stem cells revealed intra- and inter-patient transcriptional heterogeneity in pediatric acute myeloid leukemia

Cited by 7 publications

References 49 publications

Identification of Cell Type-Specific Effects of DNMT3A Mutations on Relapse in Acute Myeloid Leukemia

Identification of Cell Type-Specific Effects of DNMT3A Mutations on Relapse in Acute Myeloid Leukemia

Immunophenotypic characterization of leukemic stem cells in acute myeloid leukemia using single tube 10‐colour panel by multiparametric flow cytometry: Deciphering the spectrum, complexity and immunophenotypic heterogeneity

Emerging and Future Targeted Therapies for Pediatric Acute Myeloid Leukemia: Targeting the Leukemia Stem Cells

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