Altered mRNA expression of Pax5 and Blimp-1 in B cells in multiple myeloma.
Multiple myeloma (MM) is a plasma cell disorder that potentially initiates during an early stage of B-cell development. We encountered an unidentified isoform of B cell-specific activator protein (BSAP, or Pax5) in MM cells while performing differential analyses to compare mRNA expression in malignant and normal plasma cells. Pax5 is a transcription factor that plays a central role throughout B-cell development until the point of terminal differentiation. Our finding of this unique isoform prompted us to investigate Pax5 isoform usage in plasma cells and B-cell populations in other MM and healthy subjects. In contrast to normal Pax5 expression, we observed multiple isoforms of Pax5 in conjunction with low levels of expression of the full-length Pax5 in B cells from MM patients. The expressed isoforms in MM varied considerably from patient to patient, with no clear pattern. We also performed semiquantitative analyses of the mRNA expression levels of B lymphocyte-induced maturation protein (Blimp-1), because expression levels of Pax5 and Blimp-1 have been shown to be inversely correlated. We observed the expression of Blimp-1 in the B-cell populations in all 11 MM patients but in none of 11 healthy subjects. We hypothesize that premature Blimp-1 expression coupled to altered and deficient Pax5 expression causes some proliferating B cells to prematurely differentiate to plasma cells in MM.
Borson
Nancy D
ND
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA. borson.nancy@mayo.edu
Lacy
Martha Q
MQ
Wettstein
Peter J
PJ
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D002454:Cell Differentiation; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005091:Exons / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism; D051757:PAX5 Transcription Factor; D010950:Plasma Cells / Q000378:metabolism; D000074462:Positive Regulatory Domain I-Binding Factor 1; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012326:RNA Splicing; D012333:RNA, Messenger / Q000096:biosynthesis*; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D013382:Subtraction Technique; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012097:Repressor Proteins; D014157:Transcription Factors; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1