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• W2901356976 abstract "Decades of lack of progress in treating many fatal malignancies of the blood-forming system is commanding interest in new approaches. Targeting early events in the leukemogenic process has long been recognized as likely to offer the information required for these diseases. Analysis of the representation of different mutations in the leukemic cells from individual patients offers a retrospective method to infer their sequence of acquisition and associated subclonal dynamics. An alternative, prospective approach is to exploit strategies for recreating human leukemia de novo using defined genetic methods. This concept is not new, but has been historically difficult to realize. A brief review of our experience in generating insights into the properties and regulation of primitive normal human hematopoietic cells serves as a reminder of how this has enabled our recent advances in developing this approach using both primary sources of chronic myeloid leukemic cells and normal cord blood cells as targets. Decades of lack of progress in treating many fatal malignancies of the blood-forming system is commanding interest in new approaches. Targeting early events in the leukemogenic process has long been recognized as likely to offer the information required for these diseases. Analysis of the representation of different mutations in the leukemic cells from individual patients offers a retrospective method to infer their sequence of acquisition and associated subclonal dynamics. An alternative, prospective approach is to exploit strategies for recreating human leukemia de novo using defined genetic methods. This concept is not new, but has been historically difficult to realize. A brief review of our experience in generating insights into the properties and regulation of primitive normal human hematopoietic cells serves as a reminder of how this has enabled our recent advances in developing this approach using both primary sources of chronic myeloid leukemic cells and normal cord blood cells as targets. This perspective traces some highlights from our laboratory research efforts spanning several decades that have worked toward the long-term goal of improving outcomes of patients with acute myeloid leukemia (AML). It is also written with the purpose of formally recognizing the extraordinary insight and generosity of the Stiftelsen family and the Tobias Foundation they created. Their vision to promote hematopoietic stem cell research as a primary avenue to obtain better treatments of life-threatening blood diseases is unprecedented. Also to be recognized at the outset is the combined effort of an outstanding and dedicated team of trainees and colleagues who played a major role in the work described below. Many of the methods developed to enable primitive normal and malignant human cells to be characterized, as well as key findings thereby enabled, are due to their creativity and efforts. It is an honor and a privilege to link this jointly inspired and executed work with the Tobias Award, necessarily summarized here in very brief form." @default.
• W2901356976 created "2018-11-29" @default.
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• W2901356976 date "2018-11-01" @default.
• W2901356976 modified "2023-10-16" @default.
• W2901356976 title "A Prospective Analysis of Human Leukemogenesis" @default.
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• W2901356976 doi "https://doi.org/10.1016/j.stemcr.2018.10.016" @default.
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