NLRP3 Inflammasome Promotes the Progression of Acute Myeloid Leukemia via IL-1β Pathway

Zhong, Chaoqing; Wang, Ruiqing; Hua, Mingqiang; Zhang, Chen; Han, Fengjiao; Xu, Miao; Yang, Xinyu; Li, Guosheng; Hu, Xiang; Sun, Tao; Ji, Chunyan; Ma, Daoxin

doi:10.3389/fimmu.2021.661939

Cited by 32 publications

(30 citation statements)

References 51 publications

(103 reference statements)

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“…Inflammasomes’ contribution to acute myeloid leukemia (AML) is currently the most extensively studied among all hematological diseases. The NLRP3 inflammasome is highly activated and overexpressed in AML cells [ 40 , 41 ]. Bone marrow mononuclear cells (BMMNCs) obtained from newly diagnosed AML patients showed markedly elevated expression of the NLRP3 pathway; however, the results for specific components varied between the studies.…”

Section: Leukemiasmentioning

confidence: 99%

“…Bone marrow mononuclear cells (BMMNCs) obtained from newly diagnosed AML patients showed markedly elevated expression of the NLRP3 pathway; however, the results for specific components varied between the studies. Depending on the information source, upregulation of NLRP3, ASC, caspase-1, IL-18, and IL-1β transcripts were reported [ 40 , 41 ]. In peripheral blood mononuclear cells (PBMCs), ASC and IL-18 mRNA levels were significantly upregulated [ 41 ].…”

Section: Leukemiasmentioning

confidence: 99%

“…Moreover, separately estimated levels of IL-18 were also increased [ 41 ]. Nevertheless, the impact of IL-18 and IL-1β on AML pathogenesis is not clear, as some studies indicate either of them being more relevant [ 40 , 41 ]. In vivo, the knockout of NLRP3 attenuated leukemic burden; accordingly, neutralizing IL-1β had a similar effect [ 40 ].…”

Section: Leukemiasmentioning

confidence: 99%

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Inflammasomes—New Contributors to Blood Diseases

Tomasik

Basak

2022

IJMS

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Inflammasomes are intracellular multimeric complexes that cleave the precursors of the IL-1 family of cytokines and various proteins, found predominantly in cells of hematopoietic origin. They consist of pattern-recognition receptors, adaptor domains, and the enzymatic caspase-1 domain. Inflammasomes become activated upon stimulation by various exogenous and endogenous agents, subsequently promoting and enhancing inflammatory responses. To date, their function has been associated with numerous pathologies. Most recently, many studies have focused on inflammasomes’ contribution to hematological diseases. Due to aberrant expression levels, NLRP3, NLRP1, and NLRC4 inflammasomes were indicated as predominantly involved. The NLRP3 inflammasome correlated with the pathogenesis of non-Hodgkin lymphomas, multiple myeloma, acute myeloid leukemia, lymphoid leukemias, myelodysplastic neoplasms, graft-versus-host-disease, and sickle cell anemia. The NLRP1 inflammasome was associated with myeloma and chronic myeloid leukemia, whereas NLRC4 was associated with hemophagocytic lymphohistiocytosis. Moreover, specific gene variants of the inflammasomes were linked to disease susceptibility. Despite the incomplete understanding of these correlations and the lack of definite conclusions regarding the therapeutic utility of inflammasome inhibitors, the available results provide a valuable basis for clinical applications and precede upcoming breakthroughs in the field of innovative treatments. This review summarizes the latest knowledge on inflammasomes in hematological diseases, indicates the potential limitations of the current research approaches, and presents future perspectives.

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Section: Leukemiasmentioning

confidence: 99%

Section: Leukemiasmentioning

confidence: 99%

Section: Leukemiasmentioning

confidence: 99%

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Inflammasomes—New Contributors to Blood Diseases

Tomasik

Basak

2022

IJMS

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“…On the contrary, the role of NLRP3 inflammasome in the pathogenesis of AML is not well documented. Zhong et al showed that AML cells overexpressed NLRP3 inflammasome components and the NRLP3 inflammasome assisted in AML propagation in an IL-1β dependent manner [ 132 ]. The same authors also demonstrated immunological implications of the NLRP3 inflammasome, which is associated with an aryl-hydrocarbon receptor (AHR) contributed to AML T helper cell abnormalities [ 133 ].…”

Section: Immune Evasion In Acute Myeloid Leukemiamentioning

confidence: 99%

Microenvironmental Features Driving Immune Evasion in Myelodysplastic Syndromes and Acute Myeloid Leukemia

Barakos

Hatzimichael

2022

Diseases

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Bone marrow, besides the known functions of hematopoiesis, is an active organ of the immune system, functioning as a sanctuary for several mature immune cells. Moreover, evidence suggests that hematopoietic stem cells (the bone marrow’s functional unit) are capable of directly sensing and responding to an array of exogenous stimuli. This chronic immune stimulation is harmful to normal hematopoietic stem cells, while essential for the propagation of myeloid diseases, which show a dysregulated immune microenvironment. The bone marrow microenvironment in myelodysplastic syndromes (MDS) is characterized by chronic inflammatory activity and immune dysfunction, that drive excessive cellular death and through immune evasion assist in cancer cell expansion. Acute myeloid leukemia (AML) is another example of immune response failure, with features that augment immune evasion and suppression. In this review, we will outline some of the functions of the bone marrow with immunological significance and describe the alterations in the immune landscape of MDS and AML that drive disease progression.

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“…A recent study showed that NLRP3 inflammasome promotes AML progression in an IL-1β-dependent manner. In patient-derived samples, NLRP3 was overexpressed and highly activated in AML bone marrow leukemia cells, and this correlated with poor prognosis, and the activation of NLRP3 in AML cells promoted leukemia cell proliferation, inhibited apoptosis, and increased resistance to chemotherapy [19].…”

Section: Nlrp3 In Hematopoiesis and Leukemogenesismentioning

confidence: 99%

The Impact of NLRP3 Activation on Hematopoietic Stem Cell Transplantation

Espinoza

Kamio

Lam

et al. 2021

IJMS

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NLR family pyrin domain-containing 3 (NLRP3) is an intracellular protein that after recognizing a broad spectrum of stressors, such as microbial motifs and endogenous danger signals, promotes the activation and release of the pro-inflammatory cytokines IL-1β and IL-18, thus playing an essential role in the innate immune response. Several blood cell types, including macrophages, dendritic cells, and hematopoietic stem and progenitor cells (HSPCs), express NLRP3, where it has been implicated in various physiological and pathological processes. For example, NLRP3 participates in the development and expansion of HSPCs, and their release from bone marrow into the peripheral blood has been implicated in certain hematological disorders including various types of leukemia. In addition, accumulating evidence indicates that activation of NLRP3 plays a pivotal role in the development of transplant complications in patients receiving hematopoietic stem cell transplantation (HSCT) including graft versus host disease, severe infections, and transplant-related mortality. The majority of these complications are triggered by the severe tissue damage derived from the conditioning regimens utilized in HSCT which, in turn, activates NLRP3 and, ultimately, promotes the release of proinflammatory cytokines such as IL-1β and IL-18. Here, we summarize the implications of NLRP3 in HSCT with an emphasis on the involvement of this inflammasome component in transplant complications.

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NLRP3 Inflammasome Promotes the Progression of Acute Myeloid Leukemia via IL-1β Pathway

Cited by 32 publications

References 51 publications

Inflammasomes—New Contributors to Blood Diseases

Inflammasomes—New Contributors to Blood Diseases

Microenvironmental Features Driving Immune Evasion in Myelodysplastic Syndromes and Acute Myeloid Leukemia

The Impact of NLRP3 Activation on Hematopoietic Stem Cell Transplantation

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