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Blood, 1 July 2001, Vol. 98, No. 1, pp. 244-246
BRIEF REPORT
p16INK4a and
p15INK4b gene methylations in plasma cells from
monoclonal gammopathy of undetermined significance
Gaëlle Guillerm,
Emmanuel Gyan,
Darius Wolowiec,
Thierry Facon,
Hervé Avet-Loiseau,
Kazimierz Kuliczkowski,
Francis Bauters,
Pierre Fenaux, and
Bruno Quesnel
From the Unité Institut National de la
Santé et de la Recherche Médicale 524, Institut de
Recherche sur le Cancer de Lille (IRCL), and the Service des Maladies
du Sang, Centre Hospitalier et Universitaire (CHU) Lille, Lille,
France; the Department of Hematology, Wroclaw Medical University,
Wroclaw, Poland; and the Laboratoire d'Hématologie, CHU Nantes,
Nantes, France.
p15INK4b and p16INK4a proteins are
cell cycle regulators involved in the inhibition of G1 phase
progression. High frequency of methylation of both genes has been
reported in multiple myeloma (MM), but it remains to be determined how
and when these alterations contribute to tumorigenesis. Monoclonal
gammopathy of undetermined significance (MGUS) represents an early
disease stage in a fraction of MMs. Plasma cells from 33 patients with
MGUS and 33 patients with MM were isolated and analyzed for
p15INK4b and p16INK4a
methylation by methylation-specific polymerase chain reaction. Selective methylation was found in 19% for
p16INK4a, 36% for
p15INK4b, and 6.5% for both genes in MGUS, and
frequencies were similar in MM suggesting that methylation of these
genes is an early event, not associated with transition from MGUS to
MM. p15INK4b and
p16INK4a gene methylation might contribute to
immortalization of plasma cells rather than malignant transformation in
the natural history of MM.
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