Interstitial telomere repeats in translocations of hematopoietic disorders

Coniat, Maryvonne Busson Le; Brizard, Françoise; Smadja, NV; Maarek, Odile; Sarkissian, H. Der; Berger, Roland

doi:10.1038/sj.leu.2401876

Cited by 19 publications

(12 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4,5 JT are characterized by relocalization of the same part of a donor chromosome to several recipient chromosomes, usually arising during disease progression or in complex karyotypes, and associated with poor prognosis. 6,7 In our case JT are associated with other abnormalities of chromosome 5.…”

supporting

confidence: 48%

Unusual clonal evolution involving 5q in a case of myelodysplastic syndrome with deletion 5q 31 treated with lenalidomide

Éclache¹,

Rocha²,

Roux³

et al. 2008

Haematologica

View full text Add to dashboard Cite

Unusual clonal evolution involving 5q in a case of myelodysplastic syndrome with deletion 5q 31 treated with lenalidomideLenalidomide is a very active drug in myelodysplastic syndrome with del (5q). We report such a patient treated with this drug who developed unusual complex cytogenetic abnormalities, which were elucidated by multi-FISH and FISH analysis as jumping translocations involving the long arm of chromosome 5, that resulted in an increase of 5q copies. This unusual findings is discussed in the context of resistance to lenalidomide observed in this patient. Haematologica. 2008 Feb; 93:(2) 315-316. DOI: 10.3324/haematol.11917 The 5q-syndrome, 1 is characterized by female predominance, refractory anemia with macrocytosis, normal or elevated platelet counts, frequent erythoblastopenia, abnormal monolobulated megakaryocytes, no excess of marrow blasts count, isolated del(5)(q13q33), rare progression to overt leukemia and prolonged survival.2 Lenalidomide (Revlimid; Celgene Corporation) is a thalidomide analogue with particular activity in MDS with del(5q), especially in the 5q-syndrome, leading to transfusion independence and cytogenetic response in over two-thirds of cases.3 We report a patient with the 5q-syndrome, who had resistance to lenalidomide treatment, associated to emergence of clonal evolution involving chromosome. /L, bone marrow examination showed 4% blasts and no further dysmegakaryopoeisis but persistent dyserythropoiesis. Karyotype showed 46, XX, del(5)(q31q35) in 22 out of 26 examined metaphases. The dose of lenalidomide was increased to 10 mg once daily, 3 weeks every month. After another four months, the red blood cell transfusion requirement remained unchanged and lenalidomide was stopped. Bone marrow examination revealed erythroid hyperplasia with megaloblastoid features, decrease in granulocytes, recurrence of typical dysmegakaryopoiesis, without excess of blasts.Cytogenetic examination showed a complex karyotype with del(5)(q31q35) associated with 2-4 derivative chromosomes consisting of the long arm of chromosome 5 and variable partners as short arm: 45-46,XX, del(4)(q21q35) [7],add(5)(p10) [5],+add(5)(p10)del (5) (Figure 1). Hybridization with EGRF1 probe, showed 3 spots in 45% of cells and 4 spots in 5%. Hybridization with centromeric probes (pGA-16 and pEDZ6, a gift from S. Romana, Hopital Necker Paris) confirmed the dicentric dic(5;6) in 30% of the cells. The patient died in December 2006 from lung infection.Our patient showed no erythroid response to lenalidomide and clonal cytogenetic evolution that was unusual in the 5q-syndrome. The cytogenetic evolution with numerous 5q derivatives resulting from unbalanced translocations between different partners had not, to our knowledge, been previously described, with chromosome 5. It suggests jumping translocations (JT) rarely described in different hematologic malignancies including lymphoma, myeloma, and AML or ALL.4,5 JT are characterized by relocalization of the same part of a donor chromosome to several recipient chromosomes, ...

show abstract

supporting

confidence: 48%

Unusual clonal evolution involving 5q in a case of myelodysplastic syndrome with deletion 5q 31 treated with lenalidomide

Éclache¹,

Rocha²,

Roux³

et al. 2008

Haematologica

View full text Add to dashboard Cite

show abstract

“…Moreover, a fusion of telomeric repeats and centromeric alphoid sequences, beta satellite sequences, and low copy repeats was found in some cases (Rivera et al, 1999;Reddy and Murphy, 2000;Stankiewicz et al, 2003). On the other hand, in acquired JTs of hematopoietic disorders, interstitial telomere DNA repeats were found in only three samples but not in six other samples (Gray et al, 1997;Andreasson et al, 1998;Bernard et al, 2000;Busson-Le Coniat et al, 2000;Kakazu et al, 2000;Le Baccon et al, 2001). The different conservation of telomeric DNA repeats in constitutional and acquired chromosome abnormalities suggests different mechanisms in the two types of rearrangements.…”

Section: Resultsmentioning

confidence: 96%

Jumping translocations

Berger

Bernard

2007

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

Jumping translocations (JT) are uncommon constitutional or acquired chromosome rearrangements involving one donor and several recipient chromosomes. They occur in various pathologic conditions and the mechanism of their formation remains elusive. A review of the literature showed that the major localizations of the breakpoints of JTs in human samples are nonrandomly located in pericentromeric and telomeric regions of chromosomes. Interestingly, comparison of the localization of the chromosomal breakpoints and of presence of interstitial DNA repeats showed differences between constitutional and acquired JTs suggesting differences in the mechanisms for the genesis of JTs and their consequences.

show abstract

“…Of note is that there are increasing numbers of reports dealing with interstitial telomere repeats in translocations of acute leukemias (Hatakeyama et al, 1999; Cuthbert et al, 1999;Busson Le Coniat et al, 2000). Although the genesis and the functional consequences are still unknown, further characterization of the biological role including jumping translocations would be necessary in elucidating the signi®cance of interstitial telomere repeats in acute leukemias.…”

Section: Acute Leukemiasmentioning

confidence: 99%