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Blood, 15 December 2002, Vol. 100, No. 13, pp. 4629-4639
NEOPLASIA
Altered mRNA expression of Pax5 and Blimp-1 in B cells in
multiple myeloma
Nancy D. Borson,
Martha Q. Lacy, and
Peter J. Wettstein
From the Departments of Immunology, Hematology and
Internal Medicine, and Surgery, Mayo Clinic, Rochester, MN.
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.
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