title: 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.
authors.affiliation: Hematology Section, Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, Maryland.
authors.forename: Weixin
authors.initials: W
authors.lastname: Wang
authors.affiliation: Hematology Section, Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, Maryland.
authors.forename: Meghan
authors.initials: M
authors.lastname: Corrigan-Cummins
authors.affiliation: Hematology Section, Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, Maryland.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Barber
authors.affiliation: Hematology Section, Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, Maryland.
authors.forename: Layla M
authors.initials: LM
authors.lastname: Saleh
authors.affiliation: Multiple Myeloma Section, Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Adriana
authors.initials: A
authors.lastname: Zingone
authors.affiliation: Hematology Section, Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, Maryland.
authors.forename: Azam
authors.initials: A
authors.lastname: Ghafoor
authors.affiliation: Multiple Myeloma Section, Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Rene
authors.initials: R
authors.lastname: Costello
authors.affiliation: Multiple Myeloma Section, Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Hematology Section, Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, Maryland.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Kurlander
authors.affiliation: Multiple Myeloma Section, Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Neha
authors.initials: N
authors.lastname: Korde
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Aldo M
authors.initials: AM
authors.lastname: Roccaro
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ghobrial
authors.affiliation: Multiple Myeloma Section, Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Ola
authors.initials: O
authors.lastname: Landgren
authors.affiliation: Hematology Section, Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, Maryland. Electronic address: calvok@cc.nih.gov.
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Calvo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000378:metabolism*; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000235:genetics; D009101:Multiple Myeloma / Q000235:genetics*; D010950:Plasma Cells / Q000378:metabolism; D059016:Tumor Microenvironment / Q000235:genetics*; D055815:Young Adult
chemical_list: D035683:MicroRNAs