Dataset Information

Aberrant Levels of miRNAs in Bone Marrow Microenvironment and Peripheral Blood of Myeloma Patients and Disease Progression.

ABSTRACT: The bone marrow (BM) microenvironment of multiple myeloma (MM) is reported to play a role in the biology of disease. In this study, we found that the extracellular BM microenvironment in MM contains a unique miRNA signature detectable by miRNA microarray and quantitative real-time PCR, which is partially represented in the peripheral blood. Eleven miRNAs were significantly decreased in both BM and serum of MM patients in comparison with controls. Evaluation of these miRNAs in plasma of a separate cohort of MM patients and controls confirmed significantly aberrant levels of let-7a, let-7b, let-7i, miR-15b, miR-16, and miR-20a in both serum and plasma. We then studied the myeloma precursor diseases and found that a subset of the MM miRNAs exhibited aberrant expression in monoclonal gammopathy of undetermined significance and smoldering myeloma. miRNA analysis of enriched CD138(+) plasma cells from MM and monoclonal gammopathy of undetermined significance found that most of the validated MM BM signature miRNAs were significantly decreased in MM plasma cells. Gene expression profiling indicated that multiple targets of the decreased miRNAs found increased expression in MM plasma cells, including ATF2, HRAS, HDAC4, TGFB1, TGFBR1, and mitogen-activated protein kinases. The findings suggest that these miRNAs are detectable in aberrant levels in the peripheral blood of patients with plasma cell proliferation and may play a role in aberrant plasma cell proliferation and disease progression.

SUBMITTER: Wang W

PROVIDER: S-EPMC4630165 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Aberrant Levels of miRNAs in Bone Marrow Microenvironment and Peripheral Blood of Myeloma Patients and Disease Progression.

Wang Weixin W Corrigan-Cummins Meghan M Barber Emily A EA Saleh Layla M LM Zingone Adriana A Ghafoor Azam A Costello Rene R Zhang Yong Y Kurlander Roger J RJ Korde Neha N Roccaro Aldo M AM Ghobrial Irene M IM Landgren Ola O Calvo Katherine R KR

The Journal of molecular diagnostics : JMD 20150930 6

The bone marrow (BM) microenvironment of multiple myeloma (MM) is reported to play a role in the biology of disease. In this study, we found that the extracellular BM microenvironment in MM contains a unique miRNA signature detectable by miRNA microarray and quantitative real-time PCR, which is partially represented in the peripheral blood. Eleven miRNAs were significantly decreased in both BM and serum of MM patients in comparison with controls. Evaluation of these miRNAs in plasma of a separat ...[more]

PMID: 26433312

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Project description:BackgroundThe bone marrow is the place of hematopoiesis with a microenvironment that supports lifelong maintenance of stem cells and high proliferation. It is not surprising that this environment is also favourable for malignant cells emerging in the bone marrow or metastasizing to it. While the cellular composition of the bone marrow microenvironment has been extensively studied, the extracellular matrix and interstitial fluid components have received little attention. Since the sinusoids connect the bone marrow interstitial fluid to the circulation, it is often considered to have the same composition as peripheral blood plasma. Stark differences in the cellular composition of the bone marrow and peripheral blood with different secretory capacities would however suggest profound differences.MethodsIn this study we set out to better define if and how the bone marrow interstitial fluid (BMIF) compares to the peripheral blood plasma (PBP) and how both are remodeled during chemotherapy. We applied a multi-omic strategy to quantify the metabolite, lipid and protein components as well as the proteolytic modification of proteins to gain a comprehensive understanding of the two compartments.ResultsWe found that the bone marrow interstitial fluid is clearly distinct from peripheral blood plasma, both during active pediatric acute lymphoblastic leukemia and following induction chemotherapy. Either compartment was shaped differently by active leukemia, with the bone marrow interstitial fluid being rich in extracellular vesicle components and showing protease dysregulation while the peripheral blood plasma showed elevation of immune regulatory proteins. Following chemotherapy, the BMIF showed signs of cellular remodeling and impaired innate immune activation while the peripheral blood plasma was characterized by restored lipid homeostasis.ConclusionThis study provides a comprehensive examination of the fluid portion of the acute lymphoblastic leukemia microenvironment and finds the contribution of either microenvironment to tumourigenesis.

Dataset Information

Aberrant Levels of miRNAs in Bone Marrow Microenvironment and Peripheral Blood of Myeloma Patients and Disease Progression.

Publications

Aberrant Levels of miRNAs in Bone Marrow Microenvironment and Peripheral Blood of Myeloma Patients and Disease Progression.

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