Telomere dynamics in patients with del (5q) MDS before and under treatment with lenalidomide

被引:10
作者
Beier, Fabian [1 ,2 ,3 ]
Kharabi Masouleh, Behzad [3 ]
Buesche, Guntram [4 ]
Ventura Ferreira, Monica S. [3 ]
Schneider, Rebekka K. [3 ]
Ziegler, Patrick [3 ]
Wilop, Stefan [3 ]
Vankann, Lucia [3 ]
Gattermann, Norbert [5 ]
Platzbecker, Uwe [6 ]
Giagounidis, Aristoteles [7 ]
Goetze, Katharina S. [8 ]
Nolte, Florian [9 ]
Hofmann, Wolf-Karsten [9 ]
Haase, Detlef [10 ]
Kreipe, Hans [4 ]
Panse, Jens [3 ]
Blasco, Maria A. [2 ]
Germing, Ulrich [5 ]
Bruemmendorf, Tim H. [3 ]
机构
[1] Rhein Westfal TH Aachen, Univ Hosp, Dept Hematol Hemostaseol Oncol & Stem Cell Transp, D-52074 Aachen, Germany
[2] Spanish Natl Canc Res Ctr CNIO, Telomere & Telomerase Grp, Madrid, Spain
[3] Rhein Westfal TH Aachen, Dept Hematol Oncol & Stem Cell Transplantat, Fac Med, Aachen, Germany
[4] Hannover Med Sch, Inst Pathol, Hannover, Germany
[5] Univ Dusseldorf, Dept Hematol Oncol & Clin Immunol, Dusseldorf, Germany
[6] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Med 1, Dresden, Germany
[7] St Johannes Hosp, Dept Hematol Oncol & Clin Immunol, Duisburg, Germany
[8] Tech Univ Munich, Dept Hematol & Oncol, D-80290 Munich, Germany
[9] Univ Hosp Mannheim, Dept Internal Med 3, Mannheim, Germany
[10] Univ Hosp Gottingen, Dept Hematol & Oncol, Gottingen, Germany
基金
欧洲研究理事会;
关键词
Myelodysplastic syndromes; Del (5q); Telomere; Leukemic stem cell; MYELODYSPLASTIC SYNDROMES; STEM-CELLS; LENGTH; 5Q-SYNDROME; DEL(5Q); FISH; INVOLVEMENT; PROGRESSION; FEATURES; DELETION;
D O I
10.1016/j.leukres.2015.09.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Myelodysplastic syndrome (MDS) associated with an acquired, isolated deletion of chromosome 5q (del (5q) MDS), represent a clonal disorder of hematopoiesis and a clinically distinct entity of MDS. Treatment of del (5q) MDS with the drug lenalidomide has significantly improved quality of life leading to transfusion independence and complete cytogenetic response rates (CCR) in the majority of patients. Telomeres are located at the end of eukaryotic chromosomes and are linked to replicative history/potential as well as genetic (in) stability of hematopoietic stem cells. Here, we analyzed telomere length (TL) dynamics before and under lenalidomide treatment in the peripheral blood and/or bone marrow of del (5q) patients enrolled in the LEMON-5 study (NCT01081431). Hematopoietic cells from del (5q) MDS patients were characterized by significantly shortened TL compared to age-matched healthy controls. Telomere loss was more accelerated in patients with longer disease duration (>2 years) and more pronounced cytopenias. Sequential analysis under lenalidomide treatment revealed that previously shortened TL in peripheral blood cells was significantly "elongated" towards normal levels within the first six months suggesting a shift from clonal del (5q) cells towards normal hematopoiesis in lenalidomide treated MDS patients. Taken together our findings suggest that the development of the del (5q) clone is associated with accelerated telomere shortening at diagnosis. However, upon induction of CCR and reoccurrence of normal hematopoiesis, the lack of a persistent TL deficit argues against telomere-mediated genetic instability neither as a disease-promoting event of del (5q) MDS nor for lenalidomide mediated development of secondary primary malignancies of the hematopoietic system in responding patients. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1292 / 1298
页数:7
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