Publication

Modeling BCR-ABL and MLL-AF9 leukemia in a human bone marrow-like scaffold-based xenograft model

Sontakke, P., Carretta, M., Jaques, J., Brouwers-Vos, A. Z., Lubbers-Aalders, L., Yuan, H., de Bruijn, J. D., Martens, A. C. M., Vellenga, E., Groen, R. W. J. & Schuringa, J. J., Oct-2016, In : Leukemia. 30, 10, p. 2064-2073 10 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Sontakke, P., Carretta, M., Jaques, J., Brouwers-Vos, A. Z., Lubbers-Aalders, L., Yuan, H., ... Schuringa, J. J. (2016). Modeling BCR-ABL and MLL-AF9 leukemia in a human bone marrow-like scaffold-based xenograft model. Leukemia, 30(10), 2064-2073. https://doi.org/10.1038/leu.2016.108

Author

Sontakke, P. ; Carretta, M. ; Jaques, J. ; Brouwers-Vos, A. Z. ; Lubbers-Aalders, L. ; Yuan, H. ; de Bruijn, J. D. ; Martens, A. C. M. ; Vellenga, E. ; Groen, R. W. J. ; Schuringa, J. J. / Modeling BCR-ABL and MLL-AF9 leukemia in a human bone marrow-like scaffold-based xenograft model. In: Leukemia. 2016 ; Vol. 30, No. 10. pp. 2064-2073.

Harvard

Sontakke, P, Carretta, M, Jaques, J, Brouwers-Vos, AZ, Lubbers-Aalders, L, Yuan, H, de Bruijn, JD, Martens, ACM, Vellenga, E, Groen, RWJ & Schuringa, JJ 2016, 'Modeling BCR-ABL and MLL-AF9 leukemia in a human bone marrow-like scaffold-based xenograft model', Leukemia, vol. 30, no. 10, pp. 2064-2073. https://doi.org/10.1038/leu.2016.108

Standard

Modeling BCR-ABL and MLL-AF9 leukemia in a human bone marrow-like scaffold-based xenograft model. / Sontakke, P.; Carretta, M.; Jaques, J.; Brouwers-Vos, A. Z.; Lubbers-Aalders, L.; Yuan, H.; de Bruijn, J. D.; Martens, A. C. M.; Vellenga, E.; Groen, R. W. J.; Schuringa, J. J.

In: Leukemia, Vol. 30, No. 10, 10.2016, p. 2064-2073.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Sontakke P, Carretta M, Jaques J, Brouwers-Vos AZ, Lubbers-Aalders L, Yuan H et al. Modeling BCR-ABL and MLL-AF9 leukemia in a human bone marrow-like scaffold-based xenograft model. Leukemia. 2016 Oct;30(10):2064-2073. https://doi.org/10.1038/leu.2016.108


BibTeX

@article{8cf056e0d01c40f788a831abfe81fce7,
title = "Modeling BCR-ABL and MLL-AF9 leukemia in a human bone marrow-like scaffold-based xenograft model",
abstract = "Although NOD-SCID IL2R gamma(-/-) (NSG) xenograft mice are currently the most frequently used model to study human leukemia in vivo, the absence of a human niche severely hampers faithful recapitulation of the disease. We used NSG mice in which ceramic scaffolds seeded with human mesenchymal stromal cells were implanted to generate a human bone marrow (huBM-sc)-like niche. We observed that, in contrast to the murine bone marrow (mBM) niche, the expression of BCR-ABL or MLL-AF9 was sufficient to induce both primary acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). Stemness was preserved within the human niches as demonstrated by serial transplantation assays. Efficient engraftment of AML MLL-AF9 and blast-crisis chronic myeloid leukemia patient cells was also observed, whereby the immature blast-like phenotype was maintained in the huBM-sc niche but to a much lesser extent in mBM niches. We compared transcriptomes of leukemias derived from mBM niches versus leukemias from huBM-like scaffold-based niches, which revealed striking differences in the expression of genes associated with hypoxia, mitochondria and metabolism. Finally, we utilized the huBM-sc MLL-AF9 B-ALL model to evaluate the efficacy of the I-BET151 inhibitor in vivo. In conclusion, we have established human niche models in which the myeloid and lymphoid features of BCR-ABL(+) and MLL-AF9(+) leukemias can be studied in detail.",
keywords = "HUMAN HEMATOPOIETIC-CELLS, HYPOXIA-INDUCIBLE FACTORS, ACUTE MYELOID-LEUKEMIA, CANCER STEM-CELLS, IMMUNODEFICIENT MICE, INITIATING CELLS, NOD/SCID MICE, SYSTEM MICE, GM-CSF, BMI1",
author = "P. Sontakke and M. Carretta and J. Jaques and Brouwers-Vos, {A. Z.} and L. Lubbers-Aalders and H. Yuan and {de Bruijn}, {J. D.} and Martens, {A. C. M.} and E. Vellenga and Groen, {R. W. J.} and Schuringa, {J. J.}",
year = "2016",
month = "10",
doi = "10.1038/leu.2016.108",
language = "English",
volume = "30",
pages = "2064--2073",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "10",

}

RIS

TY - JOUR

T1 - Modeling BCR-ABL and MLL-AF9 leukemia in a human bone marrow-like scaffold-based xenograft model

AU - Sontakke, P.

AU - Carretta, M.

AU - Jaques, J.

AU - Brouwers-Vos, A. Z.

AU - Lubbers-Aalders, L.

AU - Yuan, H.

AU - de Bruijn, J. D.

AU - Martens, A. C. M.

AU - Vellenga, E.

AU - Groen, R. W. J.

AU - Schuringa, J. J.

PY - 2016/10

Y1 - 2016/10

N2 - Although NOD-SCID IL2R gamma(-/-) (NSG) xenograft mice are currently the most frequently used model to study human leukemia in vivo, the absence of a human niche severely hampers faithful recapitulation of the disease. We used NSG mice in which ceramic scaffolds seeded with human mesenchymal stromal cells were implanted to generate a human bone marrow (huBM-sc)-like niche. We observed that, in contrast to the murine bone marrow (mBM) niche, the expression of BCR-ABL or MLL-AF9 was sufficient to induce both primary acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). Stemness was preserved within the human niches as demonstrated by serial transplantation assays. Efficient engraftment of AML MLL-AF9 and blast-crisis chronic myeloid leukemia patient cells was also observed, whereby the immature blast-like phenotype was maintained in the huBM-sc niche but to a much lesser extent in mBM niches. We compared transcriptomes of leukemias derived from mBM niches versus leukemias from huBM-like scaffold-based niches, which revealed striking differences in the expression of genes associated with hypoxia, mitochondria and metabolism. Finally, we utilized the huBM-sc MLL-AF9 B-ALL model to evaluate the efficacy of the I-BET151 inhibitor in vivo. In conclusion, we have established human niche models in which the myeloid and lymphoid features of BCR-ABL(+) and MLL-AF9(+) leukemias can be studied in detail.

AB - Although NOD-SCID IL2R gamma(-/-) (NSG) xenograft mice are currently the most frequently used model to study human leukemia in vivo, the absence of a human niche severely hampers faithful recapitulation of the disease. We used NSG mice in which ceramic scaffolds seeded with human mesenchymal stromal cells were implanted to generate a human bone marrow (huBM-sc)-like niche. We observed that, in contrast to the murine bone marrow (mBM) niche, the expression of BCR-ABL or MLL-AF9 was sufficient to induce both primary acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). Stemness was preserved within the human niches as demonstrated by serial transplantation assays. Efficient engraftment of AML MLL-AF9 and blast-crisis chronic myeloid leukemia patient cells was also observed, whereby the immature blast-like phenotype was maintained in the huBM-sc niche but to a much lesser extent in mBM niches. We compared transcriptomes of leukemias derived from mBM niches versus leukemias from huBM-like scaffold-based niches, which revealed striking differences in the expression of genes associated with hypoxia, mitochondria and metabolism. Finally, we utilized the huBM-sc MLL-AF9 B-ALL model to evaluate the efficacy of the I-BET151 inhibitor in vivo. In conclusion, we have established human niche models in which the myeloid and lymphoid features of BCR-ABL(+) and MLL-AF9(+) leukemias can be studied in detail.

KW - HUMAN HEMATOPOIETIC-CELLS

KW - HYPOXIA-INDUCIBLE FACTORS

KW - ACUTE MYELOID-LEUKEMIA

KW - CANCER STEM-CELLS

KW - IMMUNODEFICIENT MICE

KW - INITIATING CELLS

KW - NOD/SCID MICE

KW - SYSTEM MICE

KW - GM-CSF

KW - BMI1

U2 - 10.1038/leu.2016.108

DO - 10.1038/leu.2016.108

M3 - Article

VL - 30

SP - 2064

EP - 2073

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 10

ER -

ID: 37853744