High frequencies of leukemia stem cells in poor-outcome childhood precursor-B acute lymphoblastic leukemias

S. Morisot; A. S. Wayne; O. Bohana-Kashtan; I. M. Kaplan; C. D. Gocke; R. Hildreth; M. Stetler-Stevenson; R. L. Walker; S. Davis; P. S. Meltzer; S. J. Wheelan; P. Brown; R. J. Jones; L. D. Shultz; C. I. Civin

doi:10.1038/leu.2010.184

High frequencies of leukemia stem cells in poor-outcome childhood precursor-B acute lymphoblastic leukemias

S. Morisot, A. S. Wayne, O. Bohana-Kashtan, I. M. Kaplan, C. D. Gocke, R. Hildreth, M. Stetler-Stevenson, R. L. Walker, S. Davis, P. S. Meltzer, S. J. Wheelan, P. Brown, R. J. Jones, L. D. Shultz, C. I. Civin

School of Medicine

Research output: Contribution to journal › Article › peer-review

45 Scopus citations

Abstract

In order to develop a xenograft model to determine the efficacy of new therapies against primary human precursor-B acute lymphoblastic leukemia (ALL) stem cells (LSCs), we used the highly immunodeficient non-obese diabetic (NOD).Cg-Prkdc^scid IL2rg^tmlWjl /SzJ (NOD-severe combined immune deficient (scid) IL2rg^-/-) mouse strain. Intravenous transplantation of 2 of 2 ALL cell lines and 9 of 14 primary ALL cases generated leukemia-like proliferations in recipient mice by 1-7 months after transplant. Leukemias were retransplantable, and the immunophenotypes, gene rearrangements and expression profiles were identical or similar to those of the original primary samples. NOD-scid mice transplanted with the same primary samples developed similar leukemias with only a slightly longer latency than did NOD-scid-IL2Rg ^-/- mice. In this highly sensitive NOD-scid-IL2Rg /-based assay, 1-100 unsorted primary human ALL cells from five of five tested patients, four of whom eventually experienced leukemia relapse, generated leukemias in recipient mice. This very high frequency of LSCs suggests that a hierarchical LSC model is not valuable for poor-outcome ALL.

Original language	English (US)
Pages (from-to)	1859-1866
Number of pages	8
Journal	Leukemia
Volume	24
Issue number	11
DOIs	https://doi.org/10.1038/leu.2010.184
State	Published - Nov 23 2010

Keywords

childhood acute lymphoblastic leukemia
leukemia stem cells
xenograft

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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10.1038/leu.2010.184

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Morisot, S., Wayne, A. S., Bohana-Kashtan, O., Kaplan, I. M., Gocke, C. D., Hildreth, R., Stetler-Stevenson, M., Walker, R. L., Davis, S., Meltzer, P. S., Wheelan, S. J., Brown, P., Jones, R. J., Shultz, L. D., & Civin, C. I. (2010). High frequencies of leukemia stem cells in poor-outcome childhood precursor-B acute lymphoblastic leukemias. Leukemia, 24(11), 1859-1866. https://doi.org/10.1038/leu.2010.184

Morisot, S, Wayne, AS, Bohana-Kashtan, O, Kaplan, IM, Gocke, CD, Hildreth, R, Stetler-Stevenson, M, Walker, RL, Davis, S, Meltzer, PS, Wheelan, SJ, Brown, P, Jones, RJ, Shultz, LD & Civin, CI 2010, 'High frequencies of leukemia stem cells in poor-outcome childhood precursor-B acute lymphoblastic leukemias', Leukemia, vol. 24, no. 11, pp. 1859-1866. https://doi.org/10.1038/leu.2010.184

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abstract = "In order to develop a xenograft model to determine the efficacy of new therapies against primary human precursor-B acute lymphoblastic leukemia (ALL) stem cells (LSCs), we used the highly immunodeficient non-obese diabetic (NOD).Cg-Prkdcscid IL2rgtmlWjl /SzJ (NOD-severe combined immune deficient (scid) IL2rg-/-) mouse strain. Intravenous transplantation of 2 of 2 ALL cell lines and 9 of 14 primary ALL cases generated leukemia-like proliferations in recipient mice by 1-7 months after transplant. Leukemias were retransplantable, and the immunophenotypes, gene rearrangements and expression profiles were identical or similar to those of the original primary samples. NOD-scid mice transplanted with the same primary samples developed similar leukemias with only a slightly longer latency than did NOD-scid-IL2Rg -/- mice. In this highly sensitive NOD-scid-IL2Rg /-based assay, 1-100 unsorted primary human ALL cells from five of five tested patients, four of whom eventually experienced leukemia relapse, generated leukemias in recipient mice. This very high frequency of LSCs suggests that a hierarchical LSC model is not valuable for poor-outcome ALL.",

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note = "Funding Information: This research was supported in part by grants from the Leukemia & Lymphoma Society (Translational Grant 6082-08), National Foundation for Cancer Research, National Institutes of Health (P01CA070970) to CIC and CA34196 to the Jackson Lab. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute and Center for Cancer Research.",

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doi = "10.1038/leu.2010.184",

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AU - Gocke, C. D.

AU - Hildreth, R.

AU - Stetler-Stevenson, M.

AU - Walker, R. L.

AU - Davis, S.

AU - Meltzer, P. S.

AU - Wheelan, S. J.

AU - Brown, P.

AU - Jones, R. J.

AU - Shultz, L. D.

AU - Civin, C. I.

N1 - Funding Information: This research was supported in part by grants from the Leukemia & Lymphoma Society (Translational Grant 6082-08), National Foundation for Cancer Research, National Institutes of Health (P01CA070970) to CIC and CA34196 to the Jackson Lab. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute and Center for Cancer Research.

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High frequencies of leukemia stem cells in poor-outcome childhood precursor-B acute lymphoblastic leukemias

Abstract

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ASJC Scopus subject areas

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