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Clinical impact of genomic characterization of 15 patients with acute megakaryoblastic leukemia-related malignancies
- Source :
- Cold Spring Harbor Molecular Case Studies
- Publication Year :
- 2020
-
Abstract
- Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia but is approximately 500 times more likely to develop in children with Down syndrome (DS) through transformation of transient abnormal myelopoiesis (TAM). This study investigates the clinical significance of genomic heterogeneity of AMKL in children with and without DS and in children with TAM. Genomic evaluation of nine patients with DS-related TAM or AMKL, and six patients with non-DS AMKL, included conventional cytogenetics and a comprehensive next-generation sequencing panel for single-nucleotide variants/indels and copy-number variants in 118 genes and fusions involving 110 genes. Recurrent gene fusions were found in all patients with non-DS, including two individuals with complex genomes and either a NUP98–KDM5A or a KMT2A–MLLT6 fusion, and the remaining harbored a CBFA2T3–GLIS2 fusion, which arose from both typical and atypical cytogenetic mechanisms. These fusions guided treatment protocols and resulted in a change in diagnosis in two patients. The nine patients with DS had constitutional trisomy 21 and somatic GATA1 mutations, and those with DS-AMKL had two to four additional clinically significant somatic mutations. Comprehensive genomic characterization provides critical information for diagnosis, risk stratification, and treatment decisions for patients with AMKL. Continued genetic and clinical characterization of these rare cancers will aid in improving patient management.
- Subjects :
- Oncology
Male
Research Report
medicine.medical_specialty
Down syndrome
Somatic cell
Karyotype
Kruppel-Like Transcription Factors
Genome
Chromosomes
Leukemoid Reaction
Acute megakaryoblastic leukemia
Leukemia, Megakaryoblastic, Acute
Internal medicine
Neoplasms
Medicine
Humans
Clinical significance
GATA1 Transcription Factor
Genetic Predisposition to Disease
Child
Leukemia
business.industry
Infant, Newborn
Myeloid leukemia
High-Throughput Nucleotide Sequencing
Infant
GATA1
General Medicine
Genomics
Histone-Lysine N-Methyltransferase
medicine.disease
acute megakaryocytic leukemia
Neoplasm Proteins
DNA-Binding Proteins
Repressor Proteins
Child, Preschool
Female
Down Syndrome
business
Trisomy
Retinoblastoma-Binding Protein 2
Myeloid-Lymphoid Leukemia Protein
Subjects
Details
- ISSN :
- 23732873
- Volume :
- 7
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Cold Spring Harbor molecular case studies
- Accession number :
- edsair.doi.dedup.....73b500b96df7dc14e24a601c4f6f168d