Triradial and quadriradial chromosomes detected in a case of B‐cell prolymphocytic leukaemia

Abstract

A 70-year-old woman, with no specific medical history, presented with a two-month history of prolonged sinusitis and 5 kg weight loss. Clinical examination revealed massive splenomegaly (21 cm below left costal margin). Her blood count showed haemoglobin concentration 87 g/l, platelet count 70 9 10 9 /l, white cell count 9Á6 9 10 9 /l and lymphocyte count 6Á83 9 10 9 /l. b2-microglobulin was elevated (17Á8 mg/l) and lactate dehydrogenase was normal. Abnormal lymphocytes with the features of prolymphocytes were detected in the blood film (55% of white blood cells, top left). These cells comprised 30% of bone marrow cells; they expressed surface membrane CD19, CD20, strong immunoglobulin (Ig) M and IgD kappa and weak CD23, and were negative for CD5, CD10 and CD200. Both morphology and immunophenotype supported a diagnosis of B-cell prolymphocytic leukaemia (B-PLL). Cytogenetic analysis of bone marrow cells showed a complex hypodiploid karyotype (40 chromosomes), with numerical and structural abnormalities and deletion of one copy of TP53, detected by fluorescence in situ hybridization (FISH), without t(11;14) IGH/CCND1 translocation. A sub-clone resulting from the duplication of this primary clone (80 chromosomes) was also detected. Interestingly, the karyogram showed dicentric and, exceptionally, triradial and quadriradial chromosomes (upper right, RHG banding) derived from chromosome 16 material. The quadriradial chromosomes incorporated two long arms (2 copies of CBFB, red probe) and two short arms (2 copies of MYH11, green probe, blue arrow bottom left) of chromosome 16. Centromeric and telomeric FISH (bottom right) clarified the structure of the multiradial (blue arrow) and dicentric chromosomes (black arrows).Triradial figures can result from partial endoreduplication, a chromatid fragment that remains associated with its sister chromatid in anaphase or an insertion of a broken chromosome into a gap formed by a chromatid break. These multiradial figures can be encountered in the very rare ICF (Immunodeficiency, Centromere instability and Facial anomalies) syndrome, which often harbours multiradial figures of chromosome 1, 9 and 16 by interchange within heterochromatic regions. These figures can also be observed following irradiation, exposure to drugs such as vincristine, or in the context of DNA hypomethylation therapy. In this patient, the multiradial figures could be explained by the chromosomal instability related to TP53 deletion.

Telomere and Centromere Staining Followed by M-FISH Improves Diagnosis of Chromosomal Instability and Its Clinical Utility

“…In light of these data, it is necessary to re-evaluate the presence of dicentric chromosomes and centric rings in cancer patients and those with genetic disorders by TC+ M-FISH. The presence of dicentric chromosomes in cancer patients and those with genetic disorders has been related to the presence of chromosomal instability, a complex karyotype, and poor clinical outcomes [44][45][46]. In a cohort of 50 cancer patients and 44 patients with genetic disorders, we re-evaluated the presence of dicentric chromosomes, centric rings, and other chromosomal aberrations to establish a reliable and robust karyotype and detect the heterogeneity or the mosaics that are known to participate in the early steps of tumorigenesis and the initiation of chromosomal instability.…”

Depletion of Trichoplein (TpMs) Causes Chromosome Mis-Segregation, DNA Damage and Chromosome Instability in Cancer Cells

“…Anaphase bridges can result from end-to-end chromosome fusion. However, triradial and quadriradial chromosomes can also form such anaphase bridges [24]. Such fusions generate dicentrics, which break apart at the telophase, leaving one daughter cell with an unbalanced translocation and the other one with a terminal deletion.…”

A Central Role of Telomere Dysfunction in the Formation of a Unique Translocation within the Sub-Telomere Region Resulting in Duplication and Partial Trisomy

“…Furthermore, the frequencies of patient cells with drastic telomere shortening were much higher compared with cells of healthy controls [ 6 ]. In the patient cells, we also found higher rates of telomere aberrations resulting in augmented telomere shortening, possibly leading to the progression of chromosome instability [ 27 , 28 ].…”