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Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias

We have described a severe combined immunodeficiency (SCID) mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined...

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Autores principales: Yan, Ying, Wieman, Eric A, Guan, Xiuqin, Jakubowski, Ann A, Steinherz, Peter G, O'Reilly, Richard J
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807866/
https://www.ncbi.nlm.nih.gov/pubmed/20040095
http://dx.doi.org/10.1186/1756-8722-2-51
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author Yan, Ying
Wieman, Eric A
Guan, Xiuqin
Jakubowski, Ann A
Steinherz, Peter G
O'Reilly, Richard J
author_facet Yan, Ying
Wieman, Eric A
Guan, Xiuqin
Jakubowski, Ann A
Steinherz, Peter G
O'Reilly, Richard J
author_sort Yan, Ying
collection PubMed
description We have described a severe combined immunodeficiency (SCID) mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL) and 66 acute myeloid leukemia (AML)) in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 45 (33.8%) displayed an aggressive growth pattern, 14 (10.5%) displayed an indolent growth pattern and 74 (55.6%) did not grow in SCID mice. The growth probability of leukemias from relapsed and/or refractory disease was nearly 3 fold higher than that from patients with newly diagnosed disease. Serial observations found that leukemic blasts from the same individual, which did not initiate tumor growth at initial presentation and/or at early relapse, may engraft and grow in the later stages of disease, suggesting that the ability of leukemia cells for engraftment and proliferation was gradually acquired following the process of leukemia progression. Nine autonomous growing leukemia cell lines were established in vitro. These displayed an aggressive proliferation pattern, suggesting a possible correlation between the capacity of human leukemia cells for autonomous proliferation in vitro and an aggressive growth potential in SCID mice. In addition, we demonstrated that patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SClD mice had a poor clinical outcome in patients with ALL as well as AML. Patients whose leukemic blasts grew indolently or whose leukemia cells failed to induce growth had a significantly longer DFS and more favorable clinical course.
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spelling pubmed-28078662010-01-19 Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias Yan, Ying Wieman, Eric A Guan, Xiuqin Jakubowski, Ann A Steinherz, Peter G O'Reilly, Richard J J Hematol Oncol Research We have described a severe combined immunodeficiency (SCID) mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL) and 66 acute myeloid leukemia (AML)) in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 45 (33.8%) displayed an aggressive growth pattern, 14 (10.5%) displayed an indolent growth pattern and 74 (55.6%) did not grow in SCID mice. The growth probability of leukemias from relapsed and/or refractory disease was nearly 3 fold higher than that from patients with newly diagnosed disease. Serial observations found that leukemic blasts from the same individual, which did not initiate tumor growth at initial presentation and/or at early relapse, may engraft and grow in the later stages of disease, suggesting that the ability of leukemia cells for engraftment and proliferation was gradually acquired following the process of leukemia progression. Nine autonomous growing leukemia cell lines were established in vitro. These displayed an aggressive proliferation pattern, suggesting a possible correlation between the capacity of human leukemia cells for autonomous proliferation in vitro and an aggressive growth potential in SCID mice. In addition, we demonstrated that patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SClD mice had a poor clinical outcome in patients with ALL as well as AML. Patients whose leukemic blasts grew indolently or whose leukemia cells failed to induce growth had a significantly longer DFS and more favorable clinical course. BioMed Central 2009-12-29 /pmc/articles/PMC2807866/ /pubmed/20040095 http://dx.doi.org/10.1186/1756-8722-2-51 Text en Copyright ©2009 Yan et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Yan, Ying
Wieman, Eric A
Guan, Xiuqin
Jakubowski, Ann A
Steinherz, Peter G
O'Reilly, Richard J
Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias
title Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias
title_full Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias
title_fullStr Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias
title_full_unstemmed Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias
title_short Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias
title_sort autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807866/
https://www.ncbi.nlm.nih.gov/pubmed/20040095
http://dx.doi.org/10.1186/1756-8722-2-51
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