Mesenchymal stem cells from multiple myeloma patients display distinct genomic profile as compared with those from normal donors.
It is an open question whether in multiple myeloma (MM) bone marrow stromal cells contain genomic alterations, which may contribute to the pathogenesis of the disease. We conducted an array-based comparative genomic hybridization (array-CGH) analysis to compare the extent of unbalanced genomic alterations in mesenchymal stem cells from 21 myeloma patients (MM-MSCs) and 12 normal donors (ND-MSCs) after in vitro culture expansion. Whereas ND-MSCs were devoid of genomic imbalances, several non-recurrent chromosomal gains and losses (>1 Mb size) were detected in MM-MSCs. Using real-time reverse transcription PCR, we found correlative deregulated expression for five genes encoded in regions for which genomic imbalances were detected using array-CGH. In addition, only MM-MSCs showed a specific pattern of 'hot-spot' regions with discrete (<1 Mb) genomic alterations, some of which were confirmed using fluorescence in situ hybridization (FISH). Within MM-MSC samples, unsupervised cluster analysis did not correlate with particular clinicobiological features of MM patients. We also explored whether cytogenetic abnormalities present in myelomatous plasma cells (PCs) were shared by matching MSCs from the same patients using FISH. All MM-MSCs were cytogenetically normal for the tested genomic alterations. Therefore we cannot support a common progenitor for myeloma PCs and MSCs.
Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, Universidad de Salamanca-CSIC, Salamanca, Spain. mgarayoa@usal.es
M
M
Garayoa
J L
JL
Garcia
C
C
Santamaria
A
A
Garcia-Gomez
J F
JF
Blanco
A
A
Pandiella
J M
JM
Hernández
F M
FM
Sanchez-Guijo
M-C
MC
del Cañizo
N C
NC
Gutiérrez
J F
JF
San Miguel
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells / Q000737:chemistry; D019070:Cell Lineage; D002478:Cells, Cultured / Q000737:chemistry; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D059630:Mesenchymal Stem Cells / Q000737:chemistry*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000737:chemistry; D020411:Oligonucleotide Array Sequence Analysis; D010950:Plasma Cells / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000737:chemistry