Clonal hematopoiesis in patients with acquired aplastic anemia [see
comments]
H van Kamp, JE Landegent, RP Jansen, R Willemze and WE Fibbe
Department of Hematology, University Medical Center, Leiden, The
Netherlands.
To determine whether patients with acquired asplastic anemia (AA) exhibit
clonal hematopoiesis, we used restriction fragment length polymorphisms of
the X-linked genes phosphoglycerate kinase (PGK1) and hypoxanthine
phosphoribosyltransferase (HPRT) and the X-linked probe M27 beta. Of the 19
female patients studied, 18 (95%) patients were informative for at least
one marker. Of these, eight patients (42%) were heterozygous for PGK1, two
(11%) for HPRT, and 16 (84%) for M27 beta. In 13 (72%) patients, a
monoclonal pattern was found. Analysis of purified cell suspensions of four
of these patients showed that both myeloid and lymphoid cells were of
monoclonal origin, indicating the involvement of an early stem cell. The
four patients who were studied at presentation all showed a monoclonal
pattern. One of these patients showed a spontaneous recovery despite
persistent clonal hematopoiesis. The presence of either clonal or
polyclonal hematopoiesis did not show a correlation with the response to
antithymocyte globulin (ATG) treatment. A relapse after ATG was also seen
in a patient exhibiting polyclonal hematopoiesis. Conversely, a monoclonal
pattern did not preclude the occurrence of a partial or complete response
to ATG. Other potential markers to study clonality, including cytogenetic
abnormalities or point mutations of the N-ras protooncogene, were not found
in any of the patients. It is concluded that patients with AA may exhibit
clonal hematopoiesis. The significance with respect to evolution to
disorders with clonal hematopoiesis like paroxysmal nocturnal
hemoglobinuria, myelodysplasia, and acute leukemia remains to be
determined.
Volume 78,
Issue 12,
pp. 3209-3214,
12/15/1991
Copyright © 1991 by The American Society of Hematology
