Double minute chromosomes in acute myeloid leukemia and myelodysplastic syndromes are associated with complex karyotype, monosomal karyotype, TP53 deletion, and TP53 mutations

Leuk Lymphoma. 2021 Oct;62(10):2466-2474. doi: 10.1080/10428194.2021.1919663. Epub 2021 Apr 27.

Abstract

Double minute chromosomes (DMs) are rare in hematologic malignancies. We presented the cytogenetic characteristics and clinical features of the largest single-center cohort of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients with DMs. A total of 2576 AML patients and 1642 MDS patients were investigated, and 30 patients (AML = 19; MDS = 11) who had DMs were followed up. DMs were more common in primary AML (94.7%) and MDS (90.9%). Monosomal karyotypes (MK) were also the main cytogenetic characteristics, like complex karyotypes (CK). AML with myelodysplasia-related changes (AML-MRC) and MDS-refractory anemia with excess blasts (MDS-RAEB) was common in this cohort. We conclude that DMs-positive AML and DMs-positive MDS are associated with older age, complex karyotypes, monosomal karyotypes, TP53 deletion and TP53 mutations. DMs are a type of chromothripsis, which can be observed by the karyotype analysis. MYC and KMT2A were the most commonly amplified genes in DMs. Most patients with DMs presented an extremely poor prognosis.

Keywords: Double minute chromosomes (DMs); TP53 mutation; acute myeloid leukemia (AML); complex karyotype (CK); monosomal karyotype (MK); myelodysplastic syndrome (MDS).

MeSH terms

  • Aged
  • Humans
  • Karyotype
  • Karyotyping
  • Leukemia, Myeloid, Acute* / diagnosis
  • Leukemia, Myeloid, Acute* / genetics
  • Mutation
  • Myelodysplastic Syndromes* / diagnosis
  • Myelodysplastic Syndromes* / genetics
  • Prognosis
  • Tumor Suppressor Protein p53 / genetics

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53