Protracted dormancy of pre-leukemic stem cells.
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Date
2015-11-01Author
Ford, AM
Mansur, MB
Furness, CL
van Delft, FW
Okamura, J
Suzuki, T
Kobayashi, H
Kaneko, Y
Greaves, M
Type
Journal Article
Metadata
Show full item recordAbstract
Cancer stem cells can escape therapeutic killing by adopting a quiescent or dormant state. The reversibility of this condition provides the potential for later recurrence or relapse, potentially many years later. We describe the genomics of a rare case of childhood BCR-ABL1-positive, B-cell precursor acute lymphoblastic leukemia that relapsed, with an acute myeloblastic leukemia immunophenotype, 22 years after the initial diagnosis, sustained remission and presumed cure. The primary and relapsed leukemias shared the identical BCR-ABL1 fusion genomic sequence and two identical immunoglobulin gene rearrangements, indicating that the relapse was a derivative of the founding clone. All other mutational changes (single-nucleotide variant and copy number alterations) were distinct in diagnostic or relapse samples. These data provide unambiguous evidence that leukemia-propagating cells, most probably pre-leukemic stem cells, can remain covert and silent but potentially reactivatable for more than two decades.
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Subject
Humans
Fusion Proteins, bcr-abl
Genes, Immunoglobulin
Gene Rearrangement
Gene Dosage
Child, Preschool
Male
Ikaros Transcription Factor
Neoplastic Stem Cells
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Exome
Research team
Biology of Childhood Leukaemia
Language
eng
Date accepted
2015-05-13
License start date
2015-11
Citation
Leukemia, 2015, 29 (11), pp. 2202 - 2207
Publisher
NATURE PUBLISHING GROUP