Tetraploidy acute myeloid leukaemia after chromosome 16 inversion

Vilches, Alba Sara; Bustamante, Aránzazu Díaz de; Sánchez-Calero, Jorge; Darnaude, María Teresa

doi:10.1136/bcr-2017-219274

Cited by 2 publications

(1 citation statement)

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“…Blast morphology is the association most frequently cited with T/NT AML and provides a morphological clue to the underlying karyotype as it is generally believed that increased DNA content is directly related to blast size [ 23 , 24 ]. These results indicate that if giant cells are found in BM aspirates the presence of T/NT karyotypes should also be considered [ 3 , 25 ]. However, the present data indicate that in some cases the T/NT nucleus is not enlarged (Case 1) or enlarged only to a very limited degree (−ACA compared with +ACA) and is thereby at risk of being missed by morphological examination alone.…”

Section: Resultsmentioning

confidence: 99%

Telomere Shortening in Hematological Malignancies with Tetraploidization—A Mechanism for Chromosomal Instability?

Kjeldsen

2017

Cancers

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Aneuploidy, the presence of an abnormal number of chromosomes in a cell, is one of the most obvious differences between normal and cancer cells. There is, however, debate on how aneuploid cells arise and whether or not they are a cause or a consequence of tumorigenesis. Further, it is important to distinguish aneuploidy (the “state” of the karyotype) from chromosomal instability (CIN; the “rate” of karyotypic change). Although CIN leads to aneuploidy, not all aneuploid cells exhibit CIN. One proposed route to aneuploid cells is through an unstable tetraploid intermediate because tetraploidy promotes chromosomal aberrations and tumorigenesis. Tetraploidy or near-tetraploidy (T/NT) (81–103 chromosomes) karyotypes with or without additional structural abnormalities have been reported in acute leukemia, T-cell and B-cell lymphomas, and solid tumors. In solid tumors it has been shown that tetraploidization can occur in response to loss of telomere protection in the early stages of tumorigenesis in colon cancer, Barrett’s esophagus, and breast and cervical cancers. In hematological malignancies T/NT karyotypes are rare and the role of telomere dysfunction for the induction of tetraploidization is less well characterized. To further our understanding of possible telomere dysfunction as a mechanism for tetrapolydization in hematological cancers we here characterized the chromosomal complement and measured the telomere content by interphase nuclei quantitative fluorescence in situ hybridization (iQFISH) in seven hematological cancer patients with T/NT karyotypes, and after cytogenetic remission. The patients were identified after a search in our local cytogenetic registry in the 5-year period between June 2012 and May 2017 among more than 12,000 analyzed adult patients in this period. One advantage of measuring telomere content by iQFISH is that it is a single-cell analysis so that the telomere content can be distinguished between normal karyotype cells and cells with T/NT karyotypes. We find that the telomeres are particularly short in cells with T/NT karyotypes as compared with normal cells, and in T/NT karyotypes harboring additional chromosomal aberrations as well. These findings suggest that telomere dysfunction in hematological malignancies may be a mechanism for tetraploidization and CIN.

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