Role of Sphingolipids in Hematological Malignancies: Lymphoproliferative Disorders

Sawai, Hirofumi; Taniguchi, Makoto; Okazaki, Toshiro

doi:10.1007/978-3-319-20750-6_2

Cited by 3 publications

(3 citation statements)

References 131 publications

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“…Alterations in sphingolipid metabolism have been implicated in many common human diseases, including hematological malignancies (for comprehensive reviews on this topic the reader should refer to [18,[50][51][52][53]). Interestingly, bioactive sphingolipid metabolism has also begun to emerge as an important factor in normal hematopoiesis.…”

Section: An Overview Of Sphingolipid Metabolismmentioning

confidence: 99%

Sphingolipids in Hematopoiesis: Exploring Their Role in Lineage Commitment

Raza

Salman

Luberto

2021

Cells

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Sphingolipids, associated enzymes, and the sphingolipid pathway are implicated in complex, multifaceted roles impacting several cell functions, such as cellular homeostasis, apoptosis, cell differentiation, and more through intrinsic and autocrine/paracrine mechanisms. Given this broad range of functions, it comes as no surprise that a large body of evidence points to important functions of sphingolipids in hematopoiesis. As the understanding of the processes that regulate hematopoiesis and of the specific characteristics that define each type of hematopoietic cells is being continuously refined, the understanding of the roles of sphingolipid metabolism in hematopoietic lineage commitment is also evolving. Recent findings indicate that sphingolipid alterations can modulate lineage commitment from stem cells all the way to megakaryocytic, erythroid, myeloid, and lymphoid cells. For instance, recent evidence points to the ability of de novo sphingolipids to regulate the stemness of hematopoietic stem cells while a substantial body of literature implicates various sphingolipids in specialized terminal differentiation, such as thrombopoiesis. This review provides a comprehensive discussion focused on the mechanisms that link sphingolipids to the commitment of hematopoietic cells to the different lineages, also highlighting yet to be resolved questions.

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Section: An Overview Of Sphingolipid Metabolismmentioning

confidence: 99%

Sphingolipids in Hematopoiesis: Exploring Their Role in Lineage Commitment

Raza

Salman

Luberto

2021

Cells

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“…Among lipids, sphingolipids, including sphingomyelin (SM), ceramide, and sphingosine‐1‐phosphate (S1P), are a class of lipids that share sphingoid base as a structural backbone. Sphingolipids have been known as structural components of cell membranes for a long time; however, recent studies have revealed that these molecules also have important biologic functions in the regulation of cell death, proliferation, migration, and autophagy (7). Furthermore, many studies suggest that the abnormalities of sphingolipid metabolism may be involved in inflammation and carcinogenesis (8).…”

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confidence: 99%

Sphingomyelin synthase 2 deficiency inhibits the induction of murine colitis‐associated colon cancer

et al. 2017

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Sphingomyelin synthase 2 (SMS2) is the synthetic enzyme of sphingomyelin (SM), which regulates membrane fluidity and microdomain structure. SMS2 plays a role in LPS-induced lung injury and inflammation; however, its role in inflammation-mediated tumorigenesis is unclear. We investigated the effect of SMS2 deficiency on dextran sodium sulfate (DSS)-induced murine colitis and found inhibition of DSS-induced inflammation in SMS2-deficient (SMS2 2/2 ) mice. DSS treatment induced a significant increase in ceramide levels, with a decrease of SM levels in SMS2 2/2 colon tissue, and demonstrated attenuation of the elevation of both inflammation-related gene expression and proinflammatory cytokines and chemokines, leukocyte infiltration, and MAPK and signal transducer and activator of transcription 3 activation. After undergoing transplantation of wild-type bone marrow, SMS2 2/2 mice also exhibited inhibition of DSS-induced inflammation in the colon, which suggested that SMS2 deficiency in bone marrow-derived immune cells was not involved in the inhibition of colitis. Finally, in an azoxymethane/DSS-induced cancer model, SMS2 deficiency significantly decreased tumor incidence in the colon. Our results demonstrate that SMS2 deficiency inhibits DSS-induced colitis and subsequent colitis-associated colon cancer via inhibition of colon epithelial cell-mediated inflammation; therefore, inhibition of SMS2 may be a potential therapeutic target for human colitis and colorectal cancer.-Ohnishi, T., Hashizume, C., Taniguchi, M., Furumoto, H., Han, J., Gao, R., Kinami, S., Kosaka, T., Okazaki, T. Sphingomyelin synthase 2 deficiency inhibits the induction of murine colitis-associated colon cancer. FASEB J. 31, 3816-3830 (2017). www.fasebj.orgIn the past decade, a positive correlation between inflammation and tumorigenesis has been identified, with supporting evidence from genetic, pharmacologic, and epidemiologic data in numerous organs, including colon, lungs, bladder, and ovaries (1, 2). Colorectal cancer (CRC) is one of the most common cancers worldwide. More than 1 million new cases of CRC are reported annually and the incidence rate has been increasing (3). Although most cases of CRC are sporadic, more than 20% of patients with inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, develop colitis-associated colon cancer (CAC) (4). Thus, IBD is recognized as an important risk factor for the development of CRC. Experimental evidence suggests that inflammatory changes create a favorable microenvironment for initiation of CAC and tumor progression (5); however, the pathogenic mechanism that links IBD and CAC is not fully understood.It has been reported that dysregulation of lipid metabolism is a crucial factor in cancer initiation and contributes to the development of CRC (6). Among lipids, sphingolipids, including sphingomyelin (SM), ceramide, and sphingosine-1-phosphate (S1P), are a class of lipids that share sphingoid base as a structural backbone. Sphingolipids have been known as structur...

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“…As briefly mentioned, SLs have long been implicated in hematological malignancies. Thorough reviews on the roles of SLs in various hematological malignancies have been published previously [ 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 ] and we strongly encourage all readers to peruse these to obtain a robust foundation for the updates we will be presenting herein.…”

Section: Introductionmentioning

confidence: 99%

Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies

Raza

Atallah²,

Luberto³

2022

IJMS

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Dysregulation of sphingolipid metabolism plays a complex role in hematological malignancies, beginning with the first historical link between sphingolipids and apoptosis discovered in HL-60 leukemic cells. Numerous manuscripts have reviewed the field including the early discoveries that jumpstarted the studies. Many studies discussed here support a role for sphingolipids, such as ceramide, in combinatorial therapeutic regimens to enhance anti-leukemic effects and reduce resistance to standard therapies. Additionally, inhibitors of specific nodes of the sphingolipid pathway, such as sphingosine kinase inhibitors, significantly reduce leukemic cell survival in various types of leukemias. Acid ceramidase inhibitors have also shown promising results in acute myeloid leukemia. As the field moves rapidly, here we aim to expand the body of literature discussed in previously published reviews by focusing on advances reported in the latter part of the last decade.

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Role of Sphingolipids in Hematological Malignancies: Lymphoproliferative Disorders

Cited by 3 publications

References 131 publications

Sphingolipids in Hematopoiesis: Exploring Their Role in Lineage Commitment

Sphingolipids in Hematopoiesis: Exploring Their Role in Lineage Commitment

Sphingomyelin synthase 2 deficiency inhibits the induction of murine colitis‐associated colon cancer

Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies

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