Instructive role of MLL-fusion proteins revealed by a model of t(4;11) pro-B acute lymphoblastic leukemia

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Instructive role of MLL-fusion proteins revealed by a model of t(4;11) pro-B acute lymphoblastic leukemia. / Lin, Shan; Luo, Roger T. ; Ptasinska, Anetta; Kerry, Jon; Assi, Salam; Wunderlich, Mark ; Lmamura, Toshihiko ; Kaberlein, Joseph J. ; Rayes, Ahmad ; Althoff, Mark J. ; Anastasi, John ; O’Brien, Maureen M. ; Meetei, Amom Ruhikanta; Milne, Thomas A.; Bonifer, Constanze; Mulloy, James; Thirman, Michael J.

In: Cancer Cell, Vol. 30, No. 5, 14.11.2016, p. 737–749.

Research output: Contribution to journalArticlepeer-review

Harvard

Lin, S, Luo, RT, Ptasinska, A, Kerry, J, Assi, S, Wunderlich, M, Lmamura, T, Kaberlein, JJ, Rayes, A, Althoff, MJ, Anastasi, J, O’Brien, MM, Meetei, AR, Milne, TA, Bonifer, C, Mulloy, J & Thirman, MJ 2016, 'Instructive role of MLL-fusion proteins revealed by a model of t(4;11) pro-B acute lymphoblastic leukemia', Cancer Cell, vol. 30, no. 5, pp. 737–749. https://doi.org/10.1016/j.ccell.2016.10.008

APA

Lin, S., Luo, R. T., Ptasinska, A., Kerry, J., Assi, S., Wunderlich, M., Lmamura, T., Kaberlein, J. J., Rayes, A., Althoff, M. J., Anastasi, J., O’Brien, M. M., Meetei, A. R., Milne, T. A., Bonifer, C., Mulloy, J., & Thirman, M. J. (2016). Instructive role of MLL-fusion proteins revealed by a model of t(4;11) pro-B acute lymphoblastic leukemia. Cancer Cell, 30(5), 737–749. https://doi.org/10.1016/j.ccell.2016.10.008

Vancouver

Author

Lin, Shan ; Luo, Roger T. ; Ptasinska, Anetta ; Kerry, Jon ; Assi, Salam ; Wunderlich, Mark ; Lmamura, Toshihiko ; Kaberlein, Joseph J. ; Rayes, Ahmad ; Althoff, Mark J. ; Anastasi, John ; O’Brien, Maureen M. ; Meetei, Amom Ruhikanta ; Milne, Thomas A. ; Bonifer, Constanze ; Mulloy, James ; Thirman, Michael J. / Instructive role of MLL-fusion proteins revealed by a model of t(4;11) pro-B acute lymphoblastic leukemia. In: Cancer Cell. 2016 ; Vol. 30, No. 5. pp. 737–749.

Bibtex

@article{93368e3c935e4734b4c7aed32c607068,
title = "Instructive role of MLL-fusion proteins revealed by a model of t(4;11) pro-B acute lymphoblastic leukemia",
abstract = "The t(4;11)(q21;q23) fuses MLL to AF4, the most common MLL-fusion partner. Here we show hat MLL fused to murine Af4, highly conserved with human AF4, produces high-titer retrovirus permitting efficient transduction of human CD34+ cells and generating a faithful model of t(4;11) proB ALL that fully recapitulates the immunophenotypic and molecular aspects of the disease. MLL-Af4 induces a B-ALL distinct from MLL-AF9 through differential genomic target binding of the fusion proteins leading to specific gene expression patterns. MLL-Af4 cells can assume a myeloid state under environmental pressure but retain lymphoid-lineage potential. Such incongruity was also observed in t(4;11) patients who evaded CD19-directed therapy by undergoing myeloid-lineage switch. Our model provides a valuable tool to unravel the pathogenesis of MLL-AF4 leukemogenesis.   ",
keywords = "MLL-AF4, acute lymphoblastic leukemi, chimeric fusion proteins, mouse models of cancer, acquired resistance to targeted therapy, species specificity of oncogenes",
author = "Shan Lin and Luo, {Roger T.} and Anetta Ptasinska and Jon Kerry and Salam Assi and Mark Wunderlich and Toshihiko Lmamura and Kaberlein, {Joseph J.} and Ahmad Rayes and Althoff, {Mark J.} and John Anastasi and O{\textquoteright}Brien, {Maureen M.} and Meetei, {Amom Ruhikanta} and Milne, {Thomas A.} and Constanze Bonifer and James Mulloy and Thirman, {Michael J.}",
year = "2016",
month = nov,
day = "14",
doi = "10.1016/j.ccell.2016.10.008",
language = "English",
volume = "30",
pages = "737–749",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Elsevier",
number = "5",

}

RIS

TY - JOUR

T1 - Instructive role of MLL-fusion proteins revealed by a model of t(4;11) pro-B acute lymphoblastic leukemia

AU - Lin, Shan

AU - Luo, Roger T.

AU - Ptasinska, Anetta

AU - Kerry, Jon

AU - Assi, Salam

AU - Wunderlich, Mark

AU - Lmamura, Toshihiko

AU - Kaberlein, Joseph J.

AU - Rayes, Ahmad

AU - Althoff, Mark J.

AU - Anastasi, John

AU - O’Brien, Maureen M.

AU - Meetei, Amom Ruhikanta

AU - Milne, Thomas A.

AU - Bonifer, Constanze

AU - Mulloy, James

AU - Thirman, Michael J.

PY - 2016/11/14

Y1 - 2016/11/14

N2 - The t(4;11)(q21;q23) fuses MLL to AF4, the most common MLL-fusion partner. Here we show hat MLL fused to murine Af4, highly conserved with human AF4, produces high-titer retrovirus permitting efficient transduction of human CD34+ cells and generating a faithful model of t(4;11) proB ALL that fully recapitulates the immunophenotypic and molecular aspects of the disease. MLL-Af4 induces a B-ALL distinct from MLL-AF9 through differential genomic target binding of the fusion proteins leading to specific gene expression patterns. MLL-Af4 cells can assume a myeloid state under environmental pressure but retain lymphoid-lineage potential. Such incongruity was also observed in t(4;11) patients who evaded CD19-directed therapy by undergoing myeloid-lineage switch. Our model provides a valuable tool to unravel the pathogenesis of MLL-AF4 leukemogenesis.   

AB - The t(4;11)(q21;q23) fuses MLL to AF4, the most common MLL-fusion partner. Here we show hat MLL fused to murine Af4, highly conserved with human AF4, produces high-titer retrovirus permitting efficient transduction of human CD34+ cells and generating a faithful model of t(4;11) proB ALL that fully recapitulates the immunophenotypic and molecular aspects of the disease. MLL-Af4 induces a B-ALL distinct from MLL-AF9 through differential genomic target binding of the fusion proteins leading to specific gene expression patterns. MLL-Af4 cells can assume a myeloid state under environmental pressure but retain lymphoid-lineage potential. Such incongruity was also observed in t(4;11) patients who evaded CD19-directed therapy by undergoing myeloid-lineage switch. Our model provides a valuable tool to unravel the pathogenesis of MLL-AF4 leukemogenesis.   

KW - MLL-AF4

KW - acute lymphoblastic leukemi

KW - chimeric fusion proteins

KW - mouse models of cancer

KW - acquired resistance to targeted therapy

KW - species specificity of oncogenes

U2 - 10.1016/j.ccell.2016.10.008

DO - 10.1016/j.ccell.2016.10.008

M3 - Article

VL - 30

SP - 737

EP - 749

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 5

ER -