A liquid biopsy to detect multidrug resistance and disease burden in multiple myeloma.

Rajeev Krishnan, S; De Rubis, G; Suen, H; Joshua, D; Lam Kwan, Y; Bebawy, M

A liquid biopsy to detect multidrug resistance and disease burden in multiple myeloma.

Rajeev Krishnan, S De Rubis, G

Suen, H Joshua, D Lam Kwan, Y Bebawy, M

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Publisher:: NATURE PUBLISHING GROUP
Publication Type:: Journal Article
Citation:: Blood cancer journal, 2020, 10, (3)
Issue Date:: 2020-03-13

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Field	Value	Language
dc.contributor.author	Rajeev Krishnan, S
dc.contributor.author	De Rubis, G https://orcid.org/0000-0001-7088-396X
dc.contributor.author	Suen, H
dc.contributor.author	Joshua, D
dc.contributor.author	Lam Kwan, Y
dc.contributor.author	Bebawy, M https://orcid.org/0000-0003-2606-921X
dc.date.accessioned	2020-07-27T06:47:34Z
dc.date.available	2020-01-03
dc.date.available	2020-07-27T06:47:34Z
dc.date.issued	2020-03-13
dc.identifier.citation	Blood cancer journal, 2020, 10, (3)
dc.identifier.issn	2044-5385
dc.identifier.issn	2044-5385
dc.identifier.uri	http://hdl.handle.net/10453/141871
dc.description.abstract	Multiple myeloma is an incurable cancer of bone marrow plasma cells, with a 5-year survival rate of 43%. Its incidence has increased by 126% since 1990. Treatment typically involves high-dose combination chemotherapy, but therapeutic response and patient survival are unpredictable and highly variable-attributed largely to the development of multidrug resistance (MDR). MDR is the simultaneous cross-resistance to a range of unrelated chemotherapeutic agents and is associated with poor prognosis and survival. Currently, no clinical procedures allow for a direct, continuous monitoring of MDR. We identified circulating large extracellular vesicles (specifically microparticles (MPs)) that can be used to monitor disease burden, disease progression and development of MDR in myeloma. These MPs differ phenotypically in the expression of four protein biomarkers: a plasma-cell marker (CD138), the MDR protein, P-glycoprotein (P-gp), the stem-cell marker (CD34); and phosphatidylserine (PS), an MP marker and mediator of cancer spread. Elevated levels of P-gp+ and PS+ MPs correlate with disease progression and treatment unresponsiveness. Furthermore, P-gp, PS and CD34 are predominantly expressed in CD138- MPs in advanced disease. In particular, a dual-positive (CD138-P-gp+CD34+) population is elevated in aggressive/unresponsive disease. Our test provides a personalised liquid biopsy with potential to address the unmet clinical need of monitoring MDR and treatment failure in myeloma.
dc.format	Electronic
dc.language	eng
dc.publisher	NATURE PUBLISHING GROUP
dc.relation.ispartof	Blood cancer journal
dc.relation.isbasedon	10.1038/s41408-020-0304-7
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1102 Cardiorespiratory Medicine and Haematology, 1112 Oncology and Carcinogenesis
dc.title	A liquid biopsy to detect multidrug resistance and disease burden in multiple myeloma.
dc.type	Journal Article
utslib.citation.volume	10
utslib.location.activity	United States
utslib.for	1102 Cardiorespiratory Medicine and Haematology
utslib.for	1112 Oncology and Carcinogenesis
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/Graduate School of Health/GSH.Pharmacy
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/Graduate School of Health
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2020-07-27T06:47:31Z
pubs.issue	3
pubs.publication-status	Published
pubs.volume	10
utslib.citation.issue	3

Abstract:

Multiple myeloma is an incurable cancer of bone marrow plasma cells, with a 5-year survival rate of 43%. Its incidence has increased by 126% since 1990. Treatment typically involves high-dose combination chemotherapy, but therapeutic response and patient survival are unpredictable and highly variable-attributed largely to the development of multidrug resistance (MDR). MDR is the simultaneous cross-resistance to a range of unrelated chemotherapeutic agents and is associated with poor prognosis and survival. Currently, no clinical procedures allow for a direct, continuous monitoring of MDR. We identified circulating large extracellular vesicles (specifically microparticles (MPs)) that can be used to monitor disease burden, disease progression and development of MDR in myeloma. These MPs differ phenotypically in the expression of four protein biomarkers: a plasma-cell marker (CD138), the MDR protein, P-glycoprotein (P-gp), the stem-cell marker (CD34); and phosphatidylserine (PS), an MP marker and mediator of cancer spread. Elevated levels of P-gp+ and PS+ MPs correlate with disease progression and treatment unresponsiveness. Furthermore, P-gp, PS and CD34 are predominantly expressed in CD138- MPs in advanced disease. In particular, a dual-positive (CD138-P-gp+CD34+) population is elevated in aggressive/unresponsive disease. Our test provides a personalised liquid biopsy with potential to address the unmet clinical need of monitoring MDR and treatment failure in myeloma.

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http://hdl.handle.net/10453/141871