Low Cell Bioenergetic Metabolism Characterizes Chronic Lymphocytic Leukemia Patients with Unfavorable Genetic Factors and with a Better Response to BTK Inhibition

Autor: Simone Mirabilii, Monica Piedimonte, Esmeralda Conte, Daniele Mirabilii, Francesca Maria Rossi, Riccardo Bomben, Antonella Zucchetto, Valter Gattei, Agostino Tafuri, Maria Rosaria Ricciardi
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Current Issues in Molecular Biology, Vol 46, Iss 6, Pp 5085-5099 (2024)
Druh dokumentu: article
ISSN: 1467-3045
1467-3037
DOI: 10.3390/cimb46060305
Popis: Chronic Lymphocytic Leukemia (CLL) is an indolent malignancy characterized by the accumulation of quiescent mature B cells. However, these cells are transcriptionally and translationally active, implicating an active metabolism. The recent literature suggests that CLL cells have an oxidative-type phenotype. Given the role of cell metabolism, which is able to influence the outcome of treatments, in other neoplasms, we aimed to assess its prognostic role in CLL patients by determining the ex vivo bioenergetic metabolic profile of CLL cells, evaluating the correlation with the patient clinical/biological characteristics and the in vivo response to BTK inhibitor treatment. Clustering analysis of primary samples identified two groups, characterized by low (CLL low) or high (CLL high) bioenergetic metabolic rates. Compared to the CLL high, CLL with lower bioenergetic metabolic rates belonged to patients characterized by a statistically significant higher white blood cell count and by unfavorable molecular genetics. More importantly, patients in the CLL low cluster displayed a better and more durable response to the BTK inhibitor ibrutinib, thus defining a bioenergetic metabolic subgroup that can benefit the most from this therapy.
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