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Journal of Hematology and Oncology

, 7:61

First Online: 20 August 2014Received: 10 June 2014Accepted: 06 August 2014DOI: 10.1186-s13045-014-0061-9

Cite this article as: Wang, L., Xiao, H., Zhang, X. et al. J Hematol Oncol 2014 7: 61. doi:10.1186-s13045-014-0061-9

Abstract

Telomeres are specific nucleoprotein structures at the ends of eukaryotic chromosomes. Telomeres and telomere-associated proteins maintain genome stability by protecting the ends of chromosomes from fusion and degradation. In normal somatic cells, the length of the telomeres gradually becomes shortened with cell division. In tumor cells, the shortening of telomeres length is accelerated under the increased proliferation pressure. However, it will be maintained at an extremely short length as the result of activation of telomerase. Significantly shortened telomeres, activation of telomerase, and altered expression of telomere-associated proteins are common features of various hematologic malignancies and are related with progression or chemotherapy resistance in these diseases. In patients who have received hematopoietic stem cell transplantation HSCT, the telomere length and the telomerase activity of the engrafted donor cells have a significant influence on HSCT outcomes. Transplantation-related factors should be taken into consideration because of their impacts on telomere homeostasis. As activation of telomerase is widespread in tumor cells, it has been employed as a target point in the treatment of neoplastic hematologic disorders. In this review, the characteristics and roles of telomeres and telomerase both in hematologic malignancies and in HSCT will be summarized. The current status of telomerase-targeted therapies utilized in the treatment of hematologic malignancies will also be reviewed.

KeywordsTelomere Telomerase Shelterin Hematologic malignancies Hematopoietic stem cell transplantation Target therapy AbbreviationsATMAtaxia telangiectasia-mutated gene

ATRAtaxia telangiectasia and Rad3

ALTAlternative lengthening of telomeres

ss DNASingle-strand DNA

ds DNADouble-strand DNA

TRF1Telomeric repeat-binding factors 1

TRF2Telomeric repeat-binding factors 2

TIN2TRF1-interacting nuclear factor 2

Rap1TRF2-interacting protein 1

POT1Protection of telomeres protein 1

TPP1POT1 and TIN2-interacting protein 1

ALAcute leukemia

AMLAcute myeloid leukemia

ALLAcute lymphoblastic leukemia

LDHLactate dehydrogenase

CRComplete remission

APLAcute promyelocytic leukemia

CLLChronic lymphocytic leukemia

UM-IGVHUnmutated immunoglobulin variable region

PFSProgression-free survival

OSOverall survival

CMLChronic myelocytic leukemia

CPChronic phase

BPBlastic phase

CCRCompletely cytogenetic remission

IMImatinib Mesylate

ECTRExtra-chromosomal telomeric repeat

APAccelerated phase

MDSMyelodysplastic syndromes

IPSSInternational Prognostic Score System

3DThree-dimensional

HSCTHematopoietic stem cell transplantation

HSCsHematopoietic stem cells

auto-HSCTAutologous hematopoietic stem cell transplantation

allo-HSCTAllogeneic hematopoietic stem cell transplantation

GVHDGraft-versus-host disease

cGVHDChronic graft-versus-host disease

aGVHDAcute graft-versus-host disease

TregRegulatory T cells

PBSCsPeripheral blood progenitor cells

t-MDS-AMLTherapy-related myelodysplasia or acute myelogenous leukemia

CTLCytotoxic T lymphocyte

GM-CSFGranulocyte-monocyte colony-stimulating factor

TLR-7Toll-like receptor-7

DCDendritic cell

MMMultiple myeloma

APTTActivated partial thromboplastin time

TKITyrosine kinase inhibitors

PP2AProtein phosphatase 2A

ATOArsenic trioxide

Electronic supplementary materialThe online version of this article doi:10.1186-s13045-014-0061-9 contains supplementary material, which is available to authorized users.

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Autor: Limengmeng Wang - Haowen Xiao - Xing Zhang - Chong Wang - He Huang

Fuente: https://link.springer.com/







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