Double minute chromosomes in acute myeloid leukemia, myelodysplastic syndromes, and chronic myelomonocytic leukemia are associated with micronuclei, MYC or MLL amplification, and complex karyotype
| Autor: | Carlos E. Bueso-Ramos, Sameer S. Talwalkar, Yang O. Huh, Guilin Tang, Joseph D. Khoury, Lynne V. Abruzzo, Maro Ohanian |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Cancer Research Myeloid Chronic myelomonocytic leukemia Biology Proto-Oncogene Proteins c-myc Young Adult 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases Complex Karyotype Genetics medicine Humans Double minute Molecular Biology Micronuclei Chromosome-Defective Aged Aged 80 and over Chromosome Aberrations Myelodysplastic syndromes Gene Amplification Myeloid leukemia Leukemia Myelomonocytic Chronic Karyotype Histone-Lysine N-Methyltransferase Middle Aged medicine.disease Leukemia Myeloid Acute 030104 developmental biology medicine.anatomical_structure Karyotyping Myelodysplastic Syndromes 030220 oncology & carcinogenesis Immunology Cancer research Myeloid-Lymphoid Leukemia Protein Female |
| Zdroj: | Cancer Genetics. 209:313-320 |
| ISSN: | 2210-7762 |
| DOI: | 10.1016/j.cancergen.2016.05.072 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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