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Scientists have identified genetic mutations that appear to be associated with treatment outcomes in patients with aplastic anemia.
When compared to unmutated patients, individuals with mutations in PIGA, BCOR, and BCORL1 tended to have better responses to immunosuppressive therapy and superior survival rates.
Other mutations—such as DNMT3A, ASXL1, and RUNX1—were associated with inferior response and survival rates.
Still, the investigators noted that clonal dynamics were “highly variable” in the patient samples they analyzed and might not necessarily have predicted outcomes.
Neal S. Young, MD, of the National Heart, Lung, and Blood Institute in Bethesda, Maryland, and his colleagues described this research in NEJM.
The team used next-generation DNA sequencing and array-based karyotyping to analyze 668 blood samples from 439 patients, including serial samples from 82 patients.
The investigators identified 249 somatic mutations in 156 patients (36%). The most common mutations occurred in the BCOR (9.3%), BCORL1 (9.3%), DNMT3A (8.4%), PIGA (7.5%), and ASXL1 (6.2%) genes.
Thirty-six percent of patients had multiple mutations. And some patients had multiple mutations in
the same genes, including PIGA, BCOR, DNMT3A, ASXL1, RUNX1, and ZRSR2.
The investigators identified clonal hematopoiesis in 47% of patients, most frequently as acquired mutations.
The team also found that, largely, the presence and number of mutations a patient had was positively correlated with the patient’s age. The exceptions were PIGA, BCOR, and BCORL1 mutations.
Patients with mutations in PIGA, BCOR, or BCORL1 had better responses to immunosuppressive therapy and better overall and progression-free survival than unmutated patients.
Other mutations were associated with worse outcomes. Patients with mutations in ASXL1, DNMT3A, TP53, RUNX1, JAK2, JAK3, or CSMD1 did not respond as well as unmutated patients to immunosuppressive therapy.
Mutations in ASXL1, DNMT3A, TP53, RUNX1, and CSMD1 were associated with worse overall survival, and mutations in ASXL1, DNMT3A, RUNX1, JAK2, and JAK3 were associated with worse progression-free survival.
The investigators also observed an increase in the size of clones with DNMT3A, ASXL1, RUNX1, or U2AF1 mutations. But the size of clones with PIGA, BCOR, or BCORL1 mutations remained stable or decreased with time. 
Photo by Graham Colm
Scientists have identified genetic mutations that appear to be associated with treatment outcomes in patients with aplastic anemia.
When compared to unmutated patients, individuals with mutations in PIGA, BCOR, and BCORL1 tended to have better responses to immunosuppressive therapy and superior survival rates.
Other mutations—such as DNMT3A, ASXL1, and RUNX1—were associated with inferior response and survival rates.
Still, the investigators noted that clonal dynamics were “highly variable” in the patient samples they analyzed and might not necessarily have predicted outcomes.
Neal S. Young, MD, of the National Heart, Lung, and Blood Institute in Bethesda, Maryland, and his colleagues described this research in NEJM.
The team used next-generation DNA sequencing and array-based karyotyping to analyze 668 blood samples from 439 patients, including serial samples from 82 patients.
The investigators identified 249 somatic mutations in 156 patients (36%). The most common mutations occurred in the BCOR (9.3%), BCORL1 (9.3%), DNMT3A (8.4%), PIGA (7.5%), and ASXL1 (6.2%) genes.
Thirty-six percent of patients had multiple mutations. And some patients had multiple mutations in
the same genes, including PIGA, BCOR, DNMT3A, ASXL1, RUNX1, and ZRSR2.
The investigators identified clonal hematopoiesis in 47% of patients, most frequently as acquired mutations.
The team also found that, largely, the presence and number of mutations a patient had was positively correlated with the patient’s age. The exceptions were PIGA, BCOR, and BCORL1 mutations.
Patients with mutations in PIGA, BCOR, or BCORL1 had better responses to immunosuppressive therapy and better overall and progression-free survival than unmutated patients.
Other mutations were associated with worse outcomes. Patients with mutations in ASXL1, DNMT3A, TP53, RUNX1, JAK2, JAK3, or CSMD1 did not respond as well as unmutated patients to immunosuppressive therapy.
Mutations in ASXL1, DNMT3A, TP53, RUNX1, and CSMD1 were associated with worse overall survival, and mutations in ASXL1, DNMT3A, RUNX1, JAK2, and JAK3 were associated with worse progression-free survival.
The investigators also observed an increase in the size of clones with DNMT3A, ASXL1, RUNX1, or U2AF1 mutations. But the size of clones with PIGA, BCOR, or BCORL1 mutations remained stable or decreased with time.
Photo by Graham Colm
Scientists have identified genetic mutations that appear to be associated with treatment outcomes in patients with aplastic anemia.
When compared to unmutated patients, individuals with mutations in PIGA, BCOR, and BCORL1 tended to have better responses to immunosuppressive therapy and superior survival rates.
Other mutations—such as DNMT3A, ASXL1, and RUNX1—were associated with inferior response and survival rates.
Still, the investigators noted that clonal dynamics were “highly variable” in the patient samples they analyzed and might not necessarily have predicted outcomes.
Neal S. Young, MD, of the National Heart, Lung, and Blood Institute in Bethesda, Maryland, and his colleagues described this research in NEJM.
The team used next-generation DNA sequencing and array-based karyotyping to analyze 668 blood samples from 439 patients, including serial samples from 82 patients.
The investigators identified 249 somatic mutations in 156 patients (36%). The most common mutations occurred in the BCOR (9.3%), BCORL1 (9.3%), DNMT3A (8.4%), PIGA (7.5%), and ASXL1 (6.2%) genes.
Thirty-six percent of patients had multiple mutations. And some patients had multiple mutations in
the same genes, including PIGA, BCOR, DNMT3A, ASXL1, RUNX1, and ZRSR2.
The investigators identified clonal hematopoiesis in 47% of patients, most frequently as acquired mutations.
The team also found that, largely, the presence and number of mutations a patient had was positively correlated with the patient’s age. The exceptions were PIGA, BCOR, and BCORL1 mutations.
Patients with mutations in PIGA, BCOR, or BCORL1 had better responses to immunosuppressive therapy and better overall and progression-free survival than unmutated patients.
Other mutations were associated with worse outcomes. Patients with mutations in ASXL1, DNMT3A, TP53, RUNX1, JAK2, JAK3, or CSMD1 did not respond as well as unmutated patients to immunosuppressive therapy.
Mutations in ASXL1, DNMT3A, TP53, RUNX1, and CSMD1 were associated with worse overall survival, and mutations in ASXL1, DNMT3A, RUNX1, JAK2, and JAK3 were associated with worse progression-free survival.
The investigators also observed an increase in the size of clones with DNMT3A, ASXL1, RUNX1, or U2AF1 mutations. But the size of clones with PIGA, BCOR, or BCORL1 mutations remained stable or decreased with time.