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Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies.

ABSTRACT: 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.

SUBMITTER: Raza Y

PROVIDER: S-EPMC9654982 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies.

Raza Yasharah Y Atallah Jane J Luberto Chiara C

International journal of molecular sciences 20221022 21

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 th ...[more]

PMID: 36361536

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Project description:The myristoylated alanine-rich C-kinase substrate (MARCKS) protein has been at the crossroads of multiple signaling pathways that govern several critical operations in normal and malignant cellular physiology. Functioning as a target of protein kinase C, MARCKS shuttles between the phosphorylated cytosolic form and the unphosphorylated plasma membrane-bound states whilst regulating several molecular partners including, but not limited to calmodulin, actin, phosphatidylinositol-4,5-bisphosphate, and phosphoinositide-3-kinase. As a result of these interactions, MARCKS directly or indirectly modulates a host of cellular functions, primarily including cytoskeletal reorganization, membrane trafficking, cell secretion, inflammatory response, cell migration, and mitosis. Recent evidence indicates that dysregulated expression of MARCKS is associated with the development and progression of hematological cancers. While it is understood that MARCKS impacts the overall carcinogenesis as well as plays a part in determining the disease outcome in blood cancers, we are still at an early stage of interpreting the pathophysiological roles of MARCKS in neoplastic disease. The situation is further complicated by contradictory reports regarding the role of phosphorylated versus an unphosphorylated form of MARCKS as an oncogene versus tumor suppressor in blood cancers. In this review, we will investigate the current body of knowledge and evolving concepts of the physical properties, molecular network, functional attributes, and the likely pathogenic roles of MARCKS in hematological malignancies. Key emphasis will also be laid upon understanding the novel mechanisms by which MARCKS determines the overall disease prognosis by playing a vital role in the induction of therapeutic resistance. Additionally, we will highlight the importance of MARCKS as a valuable therapeutic target in blood cancers and will discuss the potential of existing strategies available to tackle MARCKS-driven blood cancers.

Dataset Information

Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies.

Publications

Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies.

Similar Datasets

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