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Clonal Evolution: In Aplastic Anemia,
Which Mutations Matter?
Mutations in a specific set of
genes may predict whether
patients with aplastic anemia develop hematologic malignancies,
according to research recently
published in The New England
Journal of Medicine.
“Some mutations appear to
have a favorable impact, especially
on response to immunosuppressive therapy,” Neal S. Young, MD,
one of the study’s co-authors and
chief of the hematology branch
of the National Heart, Lung,
and Blood Institute in Bethesda,
Maryland, told ASH Clinical News.
“As only a few genes are involved
and this study was very large [for
aplastic anemia], determination
of the presence of a mutated clone
should be helpful in choosing
among therapies in [aplastic
anemia], especially for younger
patients, and reassuring patients,
especially older ones.”
Approximately 15 percent of
patients with acquired aplastic
anemia will develop late myelodysplastic syndromes (MDS), acute
myeloid leukemia (AML), or both
through a process historically
referred to as “clonal evolution.”
However, recent research has
provided evidence of clonal hematopoiesis in patients who do not
develop these malignancies, leading Tetsuichi Yoshizato, MD, and
colleagues to question whether
specific mutations are associated
with malignant transformation in
patients with aplastic anemia.
Dr. Yoshizato, of the Graduate School of Medicine at Kyoto
University in Japan, and his team
performed targeted deep sequencing of genes implicated in MDS,
AML, or both, with clonal populations of mutated cells correlated to
clinical outcomes.
The researchers obtained
blood, bone marrow, and buccal
samples from 439 patients with
aplastic anemia and analyzed a
total of 668 blood samples through
next-generation sequencing and
single-nucleotide polymorphism
(SNP)–based karyotyping. Serial
samples were available from 82
patients. The panel of 106 genes
ASHClinicalNews.org
for targeted sequencing focused
on genes known to be mutated in
other bone marrow failure conditions or myeloid cancers, including: PIGA, BCOR and BCORL1,
and DNMT3A.
The researchers found 249
somatic mutations among 156
patients (36%); 56 of those patients
(36%) demonstrated multiple mutations, rangin