Format

Send to

Choose Destination
See comment in PubMed Commons below
Cancer Genet. 2016 Jul-Aug;209(7-8):313-20. doi: 10.1016/j.cancergen.2016.05.072. Epub 2016 May 27.

Double minute chromosomes in acute myeloid leukemia, myelodysplastic syndromes, and chronic myelomonocytic leukemia are associated with micronuclei, MYC or MLL amplification, and complex karyotype.

Author information

  • 1Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: yhuh@mdanderson.org.
  • 2Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • 3Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • 4Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. Electronic address: lynne.abruzzo@osumc.edu.

Abstract

Double minute chromosomes (dmin) are small, paired chromatin bodies that lack a centromere and represent a form of extrachromosomal gene amplification. Dmin are rare in myeloid neoplasms and are generally associated with a poor prognosis. Most studies of dmin in myeloid neoplasms are case reports or small series. In the current study, we present the clinicopathologic and cytogenetic features of 22 patients with myeloid neoplasms harboring dmin. These neoplasms included acute myeloid leukemia (AML) (n = 18), myelodysplastic syndrome (MDS) (n = 3), and chronic myelomonocytic leukemia (CMML) (n = 1). The AML cases consisted of AML with myelodysplasia-related changes (n = 13) and therapy-related AML (n = 5). Dmin were detected in initial pre-therapy samples in 14 patients with AML or CMML; they were acquired during the disease course in 8 patients who had AML or MDS. The presence of dmin was associated with micronuclei (18/18; 100%), complex karyotype (17/22; 77.3%), and amplification of MYC (12/16; 75%) or MLL (4/16; 25%). Immunohistochemical staining for MYC performed on bone marrow core biopsy or clot sections revealed increased MYC protein in all 19 cases tested. Except for one patient, most patients failed to respond to risk-adapted chemotherapies. At last follow up, all patients had died of disease after a median of 5 months following dmin detection. In conclusion, dmin in myeloid neoplasms commonly harbor MYC or MLL gene amplification and manifest as micronuclei within leukemic blasts. Dmin are often associated with myelodysplasia or therapy-related disease, and complex karyotypes.

KEYWORDS:

Double minute chromosomes; MLL; MYC; acute myeloid leukemia; micronuclei; myelodysplastic syndrome

PMID:
27318442
DOI:
10.1016/j.cancergen.2016.05.072
[PubMed - in process]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center