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Article Dans Une Revue Blood Advances Année : 2017

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

Arnaud Petit

Résumé

T-cell acute lymphoblastic leukemia (T-ALL) expands in various bonemarrow (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-surfacemarker expression and decreased metabolism and cell-cycle progression, demonstrating a dormancy phenotype. Functionally, tailderived T-ALL exhibit a deficient short-term ex vivo growth and a delayed in vivo propagation. These features are noncell-autonomous because T-ALL fromtail 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.
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hal-02621994 , version 1 (26-05-2020)

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Xavier Cahu, Julien Calvo, Sandrine Poglio, Nais Prade, Benoit Colsch, et al.. Bone marrow sites differently imprint dormancy and chemoresistance to T-cell acute lymphoblastic leukemia. Blood Advances, 2017, 1 (20), pp.1760-1772. ⟨10.1182/bloodadvances.2017004960⟩. ⟨hal-02621994⟩
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