The role of CXCR4 in multiple myeloma: Cells’ journey from bone marrow to beyond

Ullah, Tomalika R.

doi:10.1016/j.jbo.2019.100253

Cited by 85 publications

(82 citation statements)

References 153 publications

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“…After Mel-P, bortezomib, and lenalidomide therapies, the plasma concentrations of HMGB1 were reduced in association with the risk of thrombosis [146,147]. CXCR4 plays an important role in proliferation, invasion, dissemination, and drug resistance in MM [148]. This indicates that its ligand HMGB1 could regulate MM physiological processes.…”

Section: Multiple Myelomamentioning

confidence: 99%

High mobility group box 1 (HMGB1): a pivotal regulator of hematopoietic malignancies

et al. 2020

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High mobility group box 1 (HMGB1) is a nonhistone chromatin-associated protein that has been widely reported to play a pivotal role in the pathogenesis of hematopoietic malignancies. As a representative damage-associated molecular pattern (DAMP), HMGB1 normally exists inside cells but can be secreted into the extracellular environment through passive or active release. Extracellular HMGB1 binds with several different receptors and interactors to mediate the proliferation, differentiation, mobilization, and senescence of hematopoietic stem cells (HSCs). HMGB1 is also involved in the formation of the inflammatory bone marrow (BM) microenvironment by activating proinflammatory signaling pathways. Moreover, HMGB1-dependent autophagy induces chemotherapy resistance in leukemia and multiple myeloma. In this review, we systematically summarize the emerging roles of HMGB1 in carcinogenesis, progression, prognosis, and potential clinical applications in different hematopoietic malignancies. In summary, targeting the regulation of HMGB1 activity in HSCs and the BM microenvironment is highly beneficial in the diagnosis and treatment of various hematopoietic malignancies.

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Section: Multiple Myelomamentioning

confidence: 99%

High mobility group box 1 (HMGB1): a pivotal regulator of hematopoietic malignancies

et al. 2020

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“…Small molecules and small peptides that target the CXCL12/CXCR4 axis pose several challenges in MM treatment. this is due to the unwanted side effects of the small molecules due to ubiquitous CXCR4 expression in different sites, with the latter often showing poor selectivity [170]. Potential mechanisms of resistance include down-regulation or internalization of surface CXCR4, heterogeneous expression in cancer cells resulting in incomplete targeting, and potential competition with locally increased CXCL12 concentrations [25].…”

Section: Cxcr4 Targeting In Hematological Tumorsmentioning

confidence: 99%

New Insights on the Emerging Genomic Landscape of CXCR4 in Cancer: A Lesson from WHIM

et al. 2020

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Deciphering the molecular alterations leading to disease initiation and progression is currently crucial to identify the most relevant targets for precision therapy in cancer patients. Cancers express a complex chemokine network influencing leucocyte infiltration and angiogenesis. Moreover, malignant cells also express a selective repertoire of chemokine receptors that sustain their growth and spread. At present, different cancer types have been shown to overexpress C-X-C chemokine receptor type 4 (CXCR4) and to respond to its ligand C-X-C motif chemokine 12 (CXCL12). The CXCL12/CXCR4 axis influences cancer biology, promoting survival, proliferation, and angiogenesis, and plays a pivotal role in directing migration of cancer cells to sites of metastases, making it a prognostic marker and a therapeutic target. More recently, mutations in the C-terminus of CXCR4 have been identified in the genomic landscape of patients affected by Waldenstrom’s macroglobulinemia, a rare B cell neoplasm. These mutations closely resemble those occurring in Warts, Hypogammaglobulinemia, Immunodeficiency, and Myelokathexis (WHIM) syndrome, an immunodeficiency associated with CXCR4 aberrant expression and activity and with chemotherapy resistance in clinical trials. In this review, we summarize the current knowledge on the relevance of CXCR4 mutations in cancer biology, focusing on its importance as predictors of clinical presentation and response to therapy.

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“…CXCR4, a G protein-coupled receptor activated by chemokine C-X-C motif ligand 12 (CXCL12), also known as stromal cell-derived factor-1 (SDF-1), is widely expressed in various cells including endothelial/epithelial cells, fibroblasts, and neurons [ 83 , 84 ]. CXCR4 is strongly expressed in various types of cancer cells, contributing to tumorigenesis and cancer progression, e.g., chemotaxis, invasion, angiogenesis, and cell proliferation [ 83 ].…”

Section: Molecular and Biological Characteristics Of Hmgb1mentioning

confidence: 99%

Role of HMGB1 in Chemotherapy-Induced Peripheral Neuropathy

Sekiguchi

Kawabata

2020

IJMS

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Chemotherapy-induced peripheral neuropathy (CIPN), one of major dose-limiting side effects of first-line chemotherapeutic agents such as paclitaxel, oxaliplatin, vincristine, and bortezomib is resistant to most of existing medicines. The molecular mechanisms of CIPN have not been fully understood. High mobility group box 1 (HMGB1), a nuclear protein, is a damage-associated molecular pattern protein now considered to function as a pro-nociceptive mediator once released to the extracellular space. Most interestingly, HMGB1 plays a key role in the development of CIPN. Soluble thrombomodulin (TMα), known to degrade HMGB1 in a thrombin-dependent manner, prevents CIPN in rodents treated with paclitaxel, oxaliplatin, or vincristine and in patients with colorectal cancer undergoing oxaliplatin-based chemotherapy. In this review, we describe the role of HMGB1 and its upstream/downstream mechanisms in the development of CIPN and show drug candidates that inhibit the HMGB1 pathway, possibly useful for prevention of CIPN.

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The role of CXCR4 in multiple myeloma: Cells’ journey from bone marrow to beyond

Cited by 85 publications

References 153 publications

High mobility group box 1 (HMGB1): a pivotal regulator of hematopoietic malignancies

High mobility group box 1 (HMGB1): a pivotal regulator of hematopoietic malignancies

New Insights on the Emerging Genomic Landscape of CXCR4 in Cancer: A Lesson from WHIM

Role of HMGB1 in Chemotherapy-Induced Peripheral Neuropathy

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