Written in Blood
of BCOR/BCORL1 mutations in the clonal
hierarchy,” they added.
Mutation profiles also differed among
patients with –7/del(7q). For example,
–7/del(7q) was a characteristic feature of
sMDS that evolved from AA (present in
63% of patients), whereas only 14 percent
of patients with pMDS had the mutation
(p value not provided). TP53 mutations
appeared to be more common in pMDS
with –7/del(7q), but ASXL1, RUNX1, TET2,
and SETBP1 mutations “appeared to
be over-represented” in sMDS with –7/
del(7q). The difference was only statisti-
cally significant for RUNX1 (p=0.003)
because of low numbers of events, the
authors reported.
The researchers then analyzed a
cohort of 21 patients with AA, eight of
whom progressed to sMDS, finding that
mutations were observed more frequently
in progressors than non-progressors
(50% vs. 8%; p=0.048). Progressors
also had a higher average number of
mutations than non-progressors (3.4 vs.
0.7; p=0.005). These data suggest “that
certain clonal events seen in MDS stage
of the disease are indeed acquired early
at presentation of AA and that some
early hits may lead to subsequent clonal
evolution,” the authors wrote, adding that
ASXL1, U2AF1, and JAK2 found at AA
presentation were also observed in MDS
progressors.
Finally, to assess the potential impact
of somatic mutations on treatment
outcomes, the researchers analyzed
a subset of AA patients (n=37) who
received IST. Clonal somatic alterations,
which were identified in six of 25
patients who responded and in four of
12 patients who were refractory to IST
treatment, did not predict the efficacy of
IST, “consistent with the transient nature
of most of these events,” the authors
wrote. They also found that patients with
AA who had any of the mutational hits
found both at initial AA presentation
and in subsequent MDS (n=4) had a
shorter median progression-free survival
(2.0 years vs. not reached; p<0.001) and
overall survival (2.6 years vs. not reached;
p=0.02), compared with patients without
somatic alterations (n=67).
“While most of these [clonal so-
matic] events, found typically in MDS,
reflect clonal hematopoiesis and do
not occur in or predict sMDS, certain
founder mutations can be found at
presentation in AA and have potential
to initiate progression to sMDS,” the
authors concluded.
The study is limited by the small
number of patients in certain cohort
analyses.
The authors report no financial
conflicts.
REFERENCE
Negoro E, Nagata Y, Clemente MJ, et al. Origins of myelodysplastic
syndromes after aplastic anemia. Blood. 2017 September 11. [Epub
ahead of print]
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