Cell-lineage level–targeted sequencing to identify acute myeloid leukemia with myelodysplasia-related changes
| Autor: | Eigo Shimizu, Sousuke Nakamura, Satoru Miyano, Mika Ito, Miho Ogawa, Nozomi Yokoyama, Tomomi Takei, Arinobu Tojo, Seiya Imoto, Kazuaki Yokoyama, Rika Kasajima, Rui Yamaguchi, Asako Kobayashi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology Male medicine.medical_specialty Myeloid Preleukemia medicine.disease_cause Translocation Genetic Myeloid Neoplasm Diagnosis Differential 03 medical and health sciences 0302 clinical medicine Gene Frequency Bone Marrow Internal medicine hemic and lymphatic diseases medicine Humans Cell Lineage Genetic Predisposition to Disease Allele frequency neoplasms Genetic Association Studies Mutation Myeloid Neoplasia business.industry Not Otherwise Specified Myeloid leukemia Genetic Variation Hematology Sequence Analysis DNA respiratory system medicine.disease Leukemia Leukemia Myeloid Acute 030104 developmental biology medicine.anatomical_structure ROC Curve 030220 oncology & carcinogenesis Myelodysplastic Syndromes Disease Progression Female business Biomarkers |
| Popis: | Acute myeloid leukemia (AML) is a clonal myeloid neoplasm that typically arises de novo; however, some cases evolve from a preleukemic state, such as myelodysplastic syndrome (MDS). Such secondary AMLs and those with typical MDS-related clinical features are known as AMLs with myelodysplasia-related changes (AML-MRC). Because patients with AML-MRC have poor prognosis, more accurate diagnostic approaches are required. In this study, we performed targeted sequencing of 54 genes in 3 cell populations (granulocyte, blast, and T-cell fractions) using samples from 13 patients with MDS, 16 patients with clinically diagnosed AML-MRC, 4 patients with suspected AML-MRC but clinically diagnosed as AML not otherwise specified (AML-NOS), and 11 patients with de novo AML. We found that overlapping mutations, defined as those shared at least by the blast and granulocyte fractions, were significantly enriched in patients with MDS and AML-MRC, including those with suspected AML-MRC, indicating a substantial history of clonal hematopoiesis. In contrast, blast-specific nonoverlapping mutations were significantly enriched in patients with de novo AML. Furthermore, the presence of overlapping mutations, excluding DNMT3A, TET2, and ASXL1, effectively segregated patients with MDS and AML-MRC or suspected AML-MRC from patients with de novo AML. Additionally, the presence of ≥3 mutations in the blast fraction was useful for distinguishing patients with AML-MRC from those with MDS. In conclusion, our approach is useful for classifying clinically diagnosable AML-MRC and identifying clinically diagnosed AML-NOS as latent AML-MRC. Additional prospective studies are needed to confirm the utility of this approach. |
| Databáze: | OpenAIRE |
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