Mesenchymal stromal cells contribute to quiescence of therapy‐resistant leukemic cells in acute myeloid leukemia

Wang, Wenwen; Bochtler, Tilmann; Wuchter, Patrick; Manta, Linda; He, Haiju; Eckstein, Volker; Ho, Anthony D.; Lutz, Christoph

doi:10.1111/ejh.12934

Cited by 8 publications

(8 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In another type of cancer, human mesenchymal stem cells (hMSC) were shown contribute to quiescence and therapy resistance of persistent acute myeloid leukemia (AML cells) [223]. In this study, quiescence is related to therapy resistance, and thus with an unwanted result.…”

Section: Favoring Quiescence (Cell Dormancy)-a Valid Therapeutic Stramentioning

confidence: 94%

CD36 and CD97 in Pancreatic Cancer versus Other Malignancies

Tănase

Gheorghișan-Gălățeanu

Popescu

et al. 2020

IJMS

View full text Add to dashboard Cite

Starting from the recent identification of CD36 and CD97 as a novel marker combination of fibroblast quiescence in lung during fibrosis, we aimed to survey the literature in search for facts about the separate (or concomitant) expression of clusters of differentiation CD36 and CD97 in either tumor- or pancreatic-cancer-associated cells. Here, we provide an account of the current knowledge on the diversity of the cellular functions of CD36 and CD97 and explore their potential (common) contributions to key cellular events in oncogenesis or metastasis development. Emphasis is placed on quiescence as an underexplored mechanism and/or potential target in therapy. Furthermore, we discuss intricate signaling mechanisms and networks involving CD36 and CD97 that may regulate different subpopulations of tumor-associated cells, such as cancer-associated fibroblasts, adipocyte-associated fibroblasts, tumor-associated macrophages, or neutrophils, during aggressive pancreatic cancer. The coexistence of quiescence and activated states in cancer-associated cell subtypes during pancreatic cancer should be better documented, in different histological forms. Remodeling of the local microenvironment may also change the balance between growth and dormant state. Taking advantage of the reported data in different other tissue types, we explore the possibility to induce quiescence (similar to that observed in normal cells), as a therapeutic option to delay the currently observed clinical outcome.

show abstract

Section: Favoring Quiescence (Cell Dormancy)-a Valid Therapeutic Stramentioning

confidence: 94%

CD36 and CD97 in Pancreatic Cancer versus Other Malignancies

Tănase

Gheorghișan-Gălățeanu

Popescu

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Cell cycle analysis was performed as described previously (17). Cells were first incubated with Human BD Fc Block (BD Pharmingen; BD Biosciences) at a final concentration of 1 µg/100 µl for 15 min at 4˚C.…”

Section: Methodsmentioning

confidence: 99%

“…DEAB treatment promotes cell cycle. As cell quiescence has been suggested to be associated with chemotherapy resistance (17), the cell cycle of pancreatic cancer cells under DEAB was analyzed. Cells treated with DEAB contained significantly decreased proportions of quiescent cells (defined as the G 0 phase) and an accumulation of cells at S-G 2 -M phases, compared with the controls (Fig.…”

Section: Malignant Proliferation Of Cancer Cells Is Weakened Under the Existence Of Deabmentioning

confidence: 99%

N,N‑diethylaminobenzaldehyde targets aldehyde dehydrogenase to eradicate human pancreatic cancer cells

Wang

Zheng

et al. 2020

Exp Ther Med

Self Cite

View full text Add to dashboard Cite

Pancreatic cancer is a common cause of worldwide cancer-related mortality with a poor 5-year survival rate. Aldehyde dehydrogenase (ALDH) activity is a possible marker for malignant stem cells in solid organ systems, including the pancreas, and N,N-diethylaminobenzaldehyde (DEAB) is able to inhibit ALDH activity. In the present study, the role of DEAB in the treatment of pancreatic cancer cells and the potential underlying mechanisms were investigated. The ALDH activities of pancreatic cancer cell lines treated with or without DEAB were analyzed by an ALDEFLUOR™ assay. The Cell Counting Kit-8 and colony formation assays, and cell cycle analysis were used to evaluate the viability, colony-forming ability and cell quiescence of cell lines under DEAB treatment, respectively. DEAB and/or gemcitabine-induced cell apoptosis was assessed by flow cytometry. DEAB reduced ALDH activity and inhibited the proliferation, colony-forming ability and cell quiescence of pancreatic cancer cell lines. Compared with respective controls, DEAB alone and the combination of gemcitabine and DEAB significantly decreased cell viability and increased cell apoptosis. Moreover, reverse transcription-PCR and western blotting were used to measure the expressions of B cell lymphoma 2 (Bcl2) associated X protein (Bax) and Bcl2 mRNA and protein. The anti-cancer effect of DEAB was associated with upregulation of Bax expression. Therefore, targeting ALDH with DEAB may be a potential therapeutic choice for pancreatic cancer, demonstrating a synergic effect with gemcitabine.

show abstract

“…Quiescence driven by the BMM is a known mediator of drug resistance in AML ( Wang et al, 2017 ) and it is now well accepted that a subpopulation of quiescent LSCs (or leukemia-initiating cells) resistant to chemotherapeutics is largely responsible for patient relapse ( Saito et al, 2010a ).…”

Section: Discussionmentioning

confidence: 99%

Recreating the Bone Marrow Microenvironment to Model Leukemic Stem Cell Quiescence

O’Reilly

Zeinabad

Nolan

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The main challenge in the treatment of acute myeloid leukemia (AML) is relapse, as it has no good treatment options and 90% of relapsed patients die as a result. It is now well accepted that relapse is due to a persisting subset of AML cells known as leukemia-initiating cells or leukemic stem cells (LSCs). Hematopoietic stem cells (HSCs) reside in the bone marrow microenvironment (BMM), a specialized niche that coordinates HSC self-renewal, proliferation, and differentiation. HSCs are divided into two types: long-term HSCs (LT-HSCs) and short-term HSCs, where LT-HSCs are typically quiescent and act as a reserve of HSCs. Like LT-HSCs, a quiescent population of LSCs also exist. Like LT-HSCs, quiescent LSCs have low metabolic activity and receive pro-survival signals from the BMM, making them resistant to drugs, and upon discontinuation of therapy, they can become activated and re-establish the disease. Several studies have shown that the activation of quiescent LSCs may sensitize them to cytotoxic drugs. However, it is very difficult to experimentally model the quiescence-inducing BMM. Here we report that culturing AML cells with bone marrow stromal cells, transforming growth factor beta-1 and hypoxia in a three-dimensional system can replicate the quiescence-driving BMM. A quiescent-like state of the AML cells was confirmed by reduced cell proliferation, increased percentage of cells in the G0 cell cycle phase and a decrease in absolute cell numbers, expression of markers of quiescence, and reduced metabolic activity. Furthermore, the culture could be established as co-axial microbeads, enabling high-throughput screening, which has been used to identify combination drug treatments that could break BMM-mediated LSC quiescence, enabling the eradication of quiescent LSCs.

show abstract

Mesenchymal stromal cells contribute to quiescence of therapy‐resistant leukemic cells in acute myeloid leukemia

Abstract: Our data suggest that hMSC contribute to quiescence and therapy resistance of persistent AML cells.

Cited by 8 publications

References 42 publications

CD36 and CD97 in Pancreatic Cancer versus Other Malignancies

CD36 and CD97 in Pancreatic Cancer versus Other Malignancies

N,N‑diethylaminobenzaldehyde targets aldehyde dehydrogenase to eradicate human pancreatic cancer cells

Recreating the Bone Marrow Microenvironment to Model Leukemic Stem Cell Quiescence

Contact Info

Product

Resources

About