Telomere deregulations possess cytogenetic, phenotype, and prognostic specificities in acute leukemias

Capraro, Valérie; Zane, Linda; Poncet, Delphine; Pérol, David; Galia, Perrine; Preudhomme, Claude; Bonnefoy, Nathalie; Gilson, Éric; Thomas, Xavier; Elhamri, Mohamed; Chelghoun, Youcef; Michallet, Mauricette; Wattel, Éric; Mortreux, Franck; Sibon, David

doi:10.1016/j.exphem.2010.10.008

Cited by 35 publications

(53 citation statements)

References 24 publications

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“…Consistent with this, TL in ALL is shorter than in AML at the time of diagnosis, though TL at time of relapse is shorter in AML than ALL (Capraro et al, 2011) and TL in ALL has been reported to be longer after treatment (Borssen et al, 2011). TL at diagnosis is shorter in B-ALL in comparison to T-ALL.…”

Section: Acute Leukaemiassupporting

confidence: 72%

“…In contrast to AML, TA is lower in ALL (Capraro et al, 2011), this probably arises as a consequence of TERT promoter methylation (Borssen et al, 2011). Consistent with this, TL in ALL is shorter than in AML at the time of diagnosis, though TL at time of relapse is shorter in AML than ALL (Capraro et al, 2011) and TL in ALL has been reported to be longer after treatment (Borssen et al, 2011).…”

Section: Acute Leukaemiassupporting

confidence: 67%

“…TA also differs between AML subtypes with M3 showing low levels in comparison to other subtypes (Xu et al, 1998;Ghaffari et al, 2008;Wang et al, 2010). TERT is known to be the ratelimiting factor for TA, and increased TA correlates with significantly increased TERT levels in AML (Xu et al, 1998;Ohyashiki et al, 2001;Capraro et al, 2011).…”

Section: Acute Leukaemiasmentioning

confidence: 99%

“…Despite this shortening, these tumours often show evidence of increased levels of TA (Ohyashiki et al, 1997a;Xu et al, 1998;Engelhardt et al, 2000;Swiggers et al, 2006;Wang et al, 2010;Capraro et al, 2011). If telomere shortening in these leukaemias is primarily driven by end-replication losses, and the presence of telomerase can slow the rate telomere shortening, then the telomere shortening in these tumours may be driven by higher levels of cell division compared to tumours exhibiting similar TLs but lower levels of TA.…”

Section: Acute Leukaemiasmentioning

confidence: 99%

“…It is now well established that telomeres are shortened in the tumour cells of patients with acute leukaemia compared with age-matched controls (Hartmann et al, 2005;Capraro et al, 2011). Despite this shortening, these tumours often show evidence of increased levels of TA (Ohyashiki et al, 1997a;Xu et al, 1998;Engelhardt et al, 2000;Swiggers et al, 2006;Wang et al, 2010;Capraro et al, 2011).…”

Section: Acute Leukaemiasmentioning

confidence: 99%

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Telomere dysfunction and its role in haematological cancer

Jones¹,

Pepper²,

Baird

2012

Br J Haematol

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SummaryObservations in human tumours, as well as mouse models, have indicated that telomere dysfunction may be a key event driving genomic instability and disease progression in many solid tumour types. In this scenario, telomere shortening ultimately results in telomere dysfunction, fusion and genomic instability, creating the large-scale rearrangements that are characteristic of these tumours. It is now becoming apparent that this paradigm may also apply to haematological malignancies; indeed these conditions have provided some of the most convincing evidence of telomere dysfunction in any malignancy. Telomere length has been shown in several malignancies to provide clinically useful prognostic information, implicating telomere dysfunction in disease progression. In these malignancies extreme telomere shortening, telomere dysfunction and fusion have all been documented and correlate with the emergence of increased genomic complexity. Telomeres may therefore represent both a clinically useful prognostic tool and a potential target for therapeutic intervention.

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Section: Acute Leukaemiassupporting

confidence: 72%

Section: Acute Leukaemiassupporting

confidence: 67%

Section: Acute Leukaemiasmentioning

confidence: 99%

Section: Acute Leukaemiasmentioning

confidence: 99%

Section: Acute Leukaemiasmentioning

confidence: 99%

See 3 more Smart Citations

Telomere dysfunction and its role in haematological cancer

Jones¹,

Pepper²,

Baird

2012

Br J Haematol

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Telomerase‐based therapies in haematological malignancies

Rafat

Asl

Mazloumi

et al. 2022

Cell Biochemistry & Function

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Telomeres are specialized genetic structures present at the end of all eukaryotic linear chromosomes. They progressively get shortened after each cell division due to end replication problems. Telomere shortening (TS) and chromosomal instability cause apoptosis and massive cell death. Following oncogene activation and inactivation of tumour suppressor genes, cells acquire mechanisms such as telomerase expression and alternative lengthening of telomeres to maintain telomere length (TL) and prevent initiation of cellular senescence or apoptosis. Significant TS, telomerase activation and alteration in expression of telomere‐associated proteins are frequent features of different haematological malignancies that reflect on the progression, response to therapy and recurrence of these diseases. Telomerase is a ribonucleoprotein enzyme that has a pivotal role in maintaining the TL. However, telomerase activity in most somatic cells is insufficient to prevent TS. In 85‐90% of tumour cells, the critically short telomeric length is maintained by telomerase activation. Thus, overexpression of telomerase in most tumour cells is a potential target for cancer therapy. In this review, alteration of telomeres, telomerase and telomere‐associated proteins in different haematological malignancies and related telomerase‐based therapies are discussed.

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The role of telomere binding molecules for normal and abnormal hematopoiesis

Hosokawa

Arai

2018

Int J Hematol

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In order to maintain the homeostasis of the hematopoietic system, hematopoietic stem cells (HSCs) need to be maintained while slowly dividing over their lifetime. However, repeated cell divisions lead to the gradual accumulation of DNA damage and ultimately impair HSC function. Since telomeres are particularly fragile when subjected to replication stress, cells have several defense machinery to protect telomeres. Moreover, HSCs must protect their genome against possible DNA damage, while maintaining telomere length. A group of proteins called the shelterin complex are deeply involved in this two-way role, and it is highly resistant to the replication stress to which HSCs are subjected. Most shelterin-deficient experimental models suffer acute cytotoxicity and severe phenotypes, as each shelterin component is essential for telomere protection. The Tin2 point mutant mice show a dyskeratosis congenita (DC) like phenotype, and the Tpp1 deletion impairs the hematopoietic system. POT1/Pot1a is highly expressed in HSCs and contributes to the maintenance of the HSC pool during in vitro culture. Here, we discuss the role of shelterin molecules in HSC regulation and review current understanding of how these are regulated in the maintenance of the HSC pool and the development of hematological disorders.

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Telomere deregulations possess cytogenetic, phenotype, and prognostic specificities in acute leukemias

Cited by 35 publications

References 24 publications

Telomere dysfunction and its role in haematological cancer

Telomere dysfunction and its role in haematological cancer

Telomerase‐based therapies in haematological malignancies

The role of telomere binding molecules for normal and abnormal hematopoiesis

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