Blood, Vol. 92 No. 9 (November 1), 1998:
pp. 3422-3427
New Somatic Mutation in the PIG-A Gene Emerges at Relapse
of Paroxysmal Nocturnal Hemoglobinuria
Khédoudja Nafa,
Monica Bessler,
H. Joachim Deeg, and
Lucio Luzzatto
From the Department of Human Genetics, Memorial Sloan-Kettering
Cancer Center, New York, NY; Department of Internal Medicine,
Washington University School of Medicine, St Louis, MO; and Fred
Hutchinson Cancer Research Center, University of Washington, Seattle,
WA.
We report a detailed longitudinal study of the first patient to be
treated (in 1973) for paroxysmal nocturnal hemoglobinuria (PNH) with
syngeneic bone marrow transplantation (BMT). The patient subsequently
relapsed with PNH in 1983, and still has PNH to date. Analysis of the
PIG-A gene in a recent blood sample showed in exon 6 an
insertion-duplication causing a frameshift. Polymerase chain reaction
(PCR) amplification of the PIG-A exon 6 from bone marrow (BM)
slides obtained before BMT showed that the duplication was not
present; instead, we found several single base pair substitutions in
exons 2 and 6. Thus, relapse of PNH in this patient was not due to
persistence of the original clones; rather, it was associated with the
emergence of a new clone. These findings support the notion that the BM
environment may create selective conditions favoring the
expansion of PNH clones.
© 1998 by The American Society of Hematology.
