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A 'telomere-associated secretory phenotype' cooperates with BCR-ABL to drive malignant proliferation of leukemic cells

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A 'telomere-associated secretory phenotype' cooperates with BCR-ABL to drive malignant proliferation of leukemic cells. / Braig, Melanie; Pällmann, N; Preukschas, M; Steinemann, D; Hofmann, W; Gompf, A; Streichert, T; Braunschweig, T; Copland, M; Rudolph, K L; Bokemeyer, C; Koschmieder, S; Schuppert, A; Balabanov, S; Brümmendorf, T H.

in: LEUKEMIA, Jahrgang 28, Nr. 10, 01.10.2014, S. 2028-39.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Braig, M, Pällmann, N, Preukschas, M, Steinemann, D, Hofmann, W, Gompf, A, Streichert, T, Braunschweig, T, Copland, M, Rudolph, KL, Bokemeyer, C, Koschmieder, S, Schuppert, A, Balabanov, S & Brümmendorf, TH 2014, 'A 'telomere-associated secretory phenotype' cooperates with BCR-ABL to drive malignant proliferation of leukemic cells', LEUKEMIA, Jg. 28, Nr. 10, S. 2028-39. https://doi.org/10.1038/leu.2014.95

APA

Braig, M., Pällmann, N., Preukschas, M., Steinemann, D., Hofmann, W., Gompf, A., Streichert, T., Braunschweig, T., Copland, M., Rudolph, K. L., Bokemeyer, C., Koschmieder, S., Schuppert, A., Balabanov, S., & Brümmendorf, T. H. (2014). A 'telomere-associated secretory phenotype' cooperates with BCR-ABL to drive malignant proliferation of leukemic cells. LEUKEMIA, 28(10), 2028-39. https://doi.org/10.1038/leu.2014.95

Vancouver

Braig M, Pällmann N, Preukschas M, Steinemann D, Hofmann W, Gompf A et al. A 'telomere-associated secretory phenotype' cooperates with BCR-ABL to drive malignant proliferation of leukemic cells. LEUKEMIA. 2014 Okt 1;28(10):2028-39. https://doi.org/10.1038/leu.2014.95

Bibtex

@article{b170bafe1bb448e3a3f0818fa2e80d7b,
title = "A 'telomere-associated secretory phenotype' cooperates with BCR-ABL to drive malignant proliferation of leukemic cells",
abstract = "Telomere biology is frequently associated with disease evolution in human cancer and dysfunctional telomeres have been demonstrated to contribute to genetic instability. In BCR-ABL(+) chronic myeloid leukemia (CML), accelerated telomere shortening has been shown to correlate with leukemia progression, risk score and response to treatment. Here, we demonstrate that proliferation of murine CML-like bone marrow cells strongly depends on telomere maintenance. CML-like cells of telomerase knockout mice with critically short telomeres (CML-iG4) are growth retarded and proliferation is terminally stalled by a robust senescent cell cycle arrest. In sharp contrast, CML-like cells with pre-shortened, but not critically short telomere lengths (CML-G2) grew most rapidly and were found to express a specific 'telomere-associated secretory phenotype', comprising secretion of chemokines, interleukins and other growth factors, thereby potentiating oncogene-driven growth. Moreover, conditioned supernatant of CML-G2 cells markedly enhanced proliferation of CML-WT and pre-senescent CML-iG4 cells. Strikingly, a similar inflammatory mRNA expression pattern was found with disease progression from chronic phase to accelerated phase in CML patients. These findings demonstrate that telomere-induced senescence needs to be bypassed by leukemic cells in order to progress to blast crisis and provide a novel mechanism by which telomere shortening may contribute to disease evolution in CML.",
keywords = "Animals, Apoptosis, Bone Marrow Cells, Cell Aging, Cell Cycle, Cell Line, Tumor, Cell Proliferation, Chemokines, Cytokines, Disease Progression, Fusion Proteins, bcr-abl, Gene Expression Regulation, Leukemic, Humans, Inflammation, Leukemia, Mice, Mice, Inbred C57BL, Mice, Knockout, Phenotype, Telomere",
author = "Melanie Braig and N P{\"a}llmann and M Preukschas and D Steinemann and W Hofmann and A Gompf and T Streichert and T Braunschweig and M Copland and Rudolph, {K L} and C Bokemeyer and S Koschmieder and A Schuppert and S Balabanov and Br{\"u}mmendorf, {T H}",
year = "2014",
month = oct,
day = "1",
doi = "10.1038/leu.2014.95",
language = "English",
volume = "28",
pages = "2028--39",
journal = "LEUKEMIA",
issn = "0887-6924",
publisher = "NATURE PUBLISHING GROUP",
number = "10",

}

RIS

TY - JOUR

T1 - A 'telomere-associated secretory phenotype' cooperates with BCR-ABL to drive malignant proliferation of leukemic cells

AU - Braig, Melanie

AU - Pällmann, N

AU - Preukschas, M

AU - Steinemann, D

AU - Hofmann, W

AU - Gompf, A

AU - Streichert, T

AU - Braunschweig, T

AU - Copland, M

AU - Rudolph, K L

AU - Bokemeyer, C

AU - Koschmieder, S

AU - Schuppert, A

AU - Balabanov, S

AU - Brümmendorf, T H

PY - 2014/10/1

Y1 - 2014/10/1

N2 - Telomere biology is frequently associated with disease evolution in human cancer and dysfunctional telomeres have been demonstrated to contribute to genetic instability. In BCR-ABL(+) chronic myeloid leukemia (CML), accelerated telomere shortening has been shown to correlate with leukemia progression, risk score and response to treatment. Here, we demonstrate that proliferation of murine CML-like bone marrow cells strongly depends on telomere maintenance. CML-like cells of telomerase knockout mice with critically short telomeres (CML-iG4) are growth retarded and proliferation is terminally stalled by a robust senescent cell cycle arrest. In sharp contrast, CML-like cells with pre-shortened, but not critically short telomere lengths (CML-G2) grew most rapidly and were found to express a specific 'telomere-associated secretory phenotype', comprising secretion of chemokines, interleukins and other growth factors, thereby potentiating oncogene-driven growth. Moreover, conditioned supernatant of CML-G2 cells markedly enhanced proliferation of CML-WT and pre-senescent CML-iG4 cells. Strikingly, a similar inflammatory mRNA expression pattern was found with disease progression from chronic phase to accelerated phase in CML patients. These findings demonstrate that telomere-induced senescence needs to be bypassed by leukemic cells in order to progress to blast crisis and provide a novel mechanism by which telomere shortening may contribute to disease evolution in CML.

AB - Telomere biology is frequently associated with disease evolution in human cancer and dysfunctional telomeres have been demonstrated to contribute to genetic instability. In BCR-ABL(+) chronic myeloid leukemia (CML), accelerated telomere shortening has been shown to correlate with leukemia progression, risk score and response to treatment. Here, we demonstrate that proliferation of murine CML-like bone marrow cells strongly depends on telomere maintenance. CML-like cells of telomerase knockout mice with critically short telomeres (CML-iG4) are growth retarded and proliferation is terminally stalled by a robust senescent cell cycle arrest. In sharp contrast, CML-like cells with pre-shortened, but not critically short telomere lengths (CML-G2) grew most rapidly and were found to express a specific 'telomere-associated secretory phenotype', comprising secretion of chemokines, interleukins and other growth factors, thereby potentiating oncogene-driven growth. Moreover, conditioned supernatant of CML-G2 cells markedly enhanced proliferation of CML-WT and pre-senescent CML-iG4 cells. Strikingly, a similar inflammatory mRNA expression pattern was found with disease progression from chronic phase to accelerated phase in CML patients. These findings demonstrate that telomere-induced senescence needs to be bypassed by leukemic cells in order to progress to blast crisis and provide a novel mechanism by which telomere shortening may contribute to disease evolution in CML.

KW - Animals

KW - Apoptosis

KW - Bone Marrow Cells

KW - Cell Aging

KW - Cell Cycle

KW - Cell Line, Tumor

KW - Cell Proliferation

KW - Chemokines

KW - Cytokines

KW - Disease Progression

KW - Fusion Proteins, bcr-abl

KW - Gene Expression Regulation, Leukemic

KW - Humans

KW - Inflammation

KW - Leukemia

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Phenotype

KW - Telomere

U2 - 10.1038/leu.2014.95

DO - 10.1038/leu.2014.95

M3 - SCORING: Journal article

C2 - 24603533

VL - 28

SP - 2028

EP - 2039

JO - LEUKEMIA

JF - LEUKEMIA

SN - 0887-6924

IS - 10

ER -