Dissecting the role of aberrant DNA methylation in human leukaemia

Giovanni Amabile; Annalisa Di Ruscio; Fabian Müller; Robert S. Welner; Henry Yang; Alexander K. Ebralidze; Hong Zhang; Elena Levantini; Lihua Qi; Giovanni Martinelli; Thijn Brummelkamp; Michelle M. Le Beau; Maria E. Figueroa; Christoph Bock; Daniel G. Tenen

doi:10.1038/ncomms8091

Dissecting the role of aberrant DNA methylation in human leukaemia

Giovanni Amabile
, Annalisa Di Ruscio
, Fabian Müller
, Robert S. Welner
, Henry Yang
, Alexander K. Ebralidze
, Hong Zhang
, Elena Levantini
, Lihua Qi
, Giovanni Martinelli
, Thijn Brummelkamp
, Michelle M. Le Beau
, Maria E. Figueroa
, Christoph Bock
, Daniel G. Tenen

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

Abstract

Chronic myeloid leukaemia (CML) is a myeloproliferative disorder characterized by the genetic translocation t(9;22)(q34;q11.2) encoding for the BCR-ABL fusion oncogene. However, many molecular mechanisms of the disease progression still remain poorly understood. A growing body of evidence suggests that the epigenetic abnormalities are involved in tyrosine kinase resistance in CML, leading to leukaemic clone escape and disease propagation. Here we show that, by applying cellular reprogramming to primary CML cells, aberrant DNA methylation contributes to the disease evolution. Importantly, using a BCR-ABL inducible murine model, we demonstrate that a single oncogenic lesion triggers DNA methylation changes, which in turn act as a precipitating event in leukaemia progression.

Lingua originale	Inglese
Numero di articolo	7091
Rivista	Nature Communications
Volume	6
DOI	https://doi.org/10.1038/ncomms8091
Stato di pubblicazione	Pubblicato - 22 mag 2015
Pubblicato esternamente	Sì

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10.1038/ncomms8091

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title = "Dissecting the role of aberrant DNA methylation in human leukaemia",

abstract = "Chronic myeloid leukaemia (CML) is a myeloproliferative disorder characterized by the genetic translocation t(9;22)(q34;q11.2) encoding for the BCR-ABL fusion oncogene. However, many molecular mechanisms of the disease progression still remain poorly understood. A growing body of evidence suggests that the epigenetic abnormalities are involved in tyrosine kinase resistance in CML, leading to leukaemic clone escape and disease propagation. Here we show that, by applying cellular reprogramming to primary CML cells, aberrant DNA methylation contributes to the disease evolution. Importantly, using a BCR-ABL inducible murine model, we demonstrate that a single oncogenic lesion triggers DNA methylation changes, which in turn act as a precipitating event in leukaemia progression.",

author = "Giovanni Amabile and \{Di Ruscio\}, Annalisa and Fabian M{\"u}ller and Welner, \{Robert S.\} and Henry Yang and Ebralidze, \{Alexander K.\} and Hong Zhang and Elena Levantini and Lihua Qi and Giovanni Martinelli and Thijn Brummelkamp and \{Le Beau\}, \{Michelle M.\} and Figueroa, \{Maria E.\} and Christoph Bock and Tenen, \{Daniel G.\}",

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month = may,

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doi = "10.1038/ncomms8091",

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AU - Amabile, Giovanni

AU - Di Ruscio, Annalisa

AU - Müller, Fabian

AU - Welner, Robert S.

AU - Yang, Henry

AU - Ebralidze, Alexander K.

AU - Zhang, Hong

AU - Levantini, Elena

AU - Qi, Lihua

AU - Martinelli, Giovanni

AU - Brummelkamp, Thijn

AU - Le Beau, Michelle M.

AU - Figueroa, Maria E.

AU - Bock, Christoph

AU - Tenen, Daniel G.

PY - 2015/5/22

Y1 - 2015/5/22

N2 - Chronic myeloid leukaemia (CML) is a myeloproliferative disorder characterized by the genetic translocation t(9;22)(q34;q11.2) encoding for the BCR-ABL fusion oncogene. However, many molecular mechanisms of the disease progression still remain poorly understood. A growing body of evidence suggests that the epigenetic abnormalities are involved in tyrosine kinase resistance in CML, leading to leukaemic clone escape and disease propagation. Here we show that, by applying cellular reprogramming to primary CML cells, aberrant DNA methylation contributes to the disease evolution. Importantly, using a BCR-ABL inducible murine model, we demonstrate that a single oncogenic lesion triggers DNA methylation changes, which in turn act as a precipitating event in leukaemia progression.

AB - Chronic myeloid leukaemia (CML) is a myeloproliferative disorder characterized by the genetic translocation t(9;22)(q34;q11.2) encoding for the BCR-ABL fusion oncogene. However, many molecular mechanisms of the disease progression still remain poorly understood. A growing body of evidence suggests that the epigenetic abnormalities are involved in tyrosine kinase resistance in CML, leading to leukaemic clone escape and disease propagation. Here we show that, by applying cellular reprogramming to primary CML cells, aberrant DNA methylation contributes to the disease evolution. Importantly, using a BCR-ABL inducible murine model, we demonstrate that a single oncogenic lesion triggers DNA methylation changes, which in turn act as a precipitating event in leukaemia progression.

UR - https://www.scopus.com/pages/publications/84930225198

U2 - 10.1038/ncomms8091

DO - 10.1038/ncomms8091

M3 - Article

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 7091

ER -

Dissecting the role of aberrant DNA methylation in human leukaemia

Abstract

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