Scientific article
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English

Bone marrow sites differently imprint dormancy and chemoresistance to T-cell acute lymphoblastic leukemia

Published inBlood advances, vol. 1, no. 20, p. 1760-1772
Publication date2017-09-12
First online date2017-09-08
Abstract

T-cell acute lymphoblastic leukemia (T-ALL) expands in various bone marrow (BM) sites of the body. We investigated whether different BM sites could differently modulate T-ALL propagation using in vivo animal models. We observed that mouse and human T-ALL develop slowly in the BM of tail vertebrae compared with the BM from thorax vertebrae. T-ALL recovered from tail BM displays lower cell-surface marker expression and decreased metabolism and cell-cycle progression, demonstrating a dormancy phenotype. Functionally, tail-derived T-ALL exhibit a deficient short-term ex vivo growth and a delayed in vivo propagation. These features are noncell-autonomous because T-ALL from tail and thorax shares identical genomic abnormalities and functional disparities disappear in vivo and in prolonged in vitro assays. Importantly tail-derived T-ALL displays higher intrinsic resistance to cell-cycle-related drugs (ie, vincristine sulfate and cytarabine). Of note, T-ALL recovered from gonadal adipose tissues or from cocultures with adipocytes shares metabolic, cell-cycle, and phenotypic or chemoresistance features, with tail-derived T-ALL suggesting adipocytes may participate in the tail BM imprints on T-ALL. Altogether these results demonstrate that BM sites differentially orchestrate T-ALL propagation stamping specific features to leukemic cells such as quiescence and decreased response to cell-cycle-dependent chemotherapy.

Keywords
  • Adult t-cell lymphoma/leukemia
  • T-cell leukemia
  • Acute
  • Mice
Affiliation entities Not a UNIGE publication
Citation (ISO format)
CAHU, Xavier et al. Bone marrow sites differently imprint dormancy and chemoresistance to T-cell acute lymphoblastic leukemia. In: Blood advances, 2017, vol. 1, n° 20, p. 1760–1772. doi: 10.1182/bloodadvances.2017004960
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Article (Published version)
Identifiers
Journal ISSN2473-9529
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