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Research Article Free access | 10.1172/JCI118474

Stroma-supported culture in childhood B-lineage acute lymphoblastic leukemia cells predicts treatment outcome.

M Kumagai, A Manabe, C H Pui, F G Behm, S C Raimondi, M L Hancock, H Mahmoud, W M Crist, and D Campana

Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101, USA.

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Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101, USA.

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Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101, USA.

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Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101, USA.

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Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101, USA.

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Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101, USA.

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Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101, USA.

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Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101, USA.

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Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101, USA.

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Published February 1, 1996 - More info

Published in Volume 97, Issue 3 on February 1, 1996
J Clin Invest. 1996;97(3):755–760. https://doi.org/10.1172/JCI118474.
© 1996 The American Society for Clinical Investigation
Published February 1, 1996 - Version history
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Abstract

We developed a stroma cell culture system that suppresses apoptosis of malignant cells from cases of B-lineage acute lymphoblastic leukemia. By multiparameter flow cytometric measurements of cell recovery after culture on stromal layers, we assessed the growth potential of 70 cases of newly diagnosed B-lineage acute lymphoblastic leukemia and related the findings of treatment outcome in a single program of chemotherapy. The numbers of leukemic cells recovered after 7 d of culture ranged from < 1 to 292% (median, 91%). The basis of poor cell recoveries from stromal layers appeared to be a propensity of the lymphoblasts to undergo apoptosis. The probability of event-free survival at 4 yr of follow-up was 50 +/- 9% (SE) among patients with higher cell recoveries ( > 91%), and 94 +/- 6% among those with reduced cell recoveries (+/- 91%; P = 0.0003). The prognostic value of leukemic cell recovery after culture exceeded estimates for all other recognized high-risk features and remained the most significant after adjustment with all competing covariates. Thus, the survival ability of leukemic cells on bone marrow-derived stromal layers reflects aggressiveness of the disease and is a powerful, independent predictor of treatment outcome in children with B-lineage acute lymphoblastic leukemia.

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