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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

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

by
Simone Mirabilii
1,*,†,
Monica Piedimonte
1,†,
Esmeralda Conte
1,
Daniele Mirabilii
2,
Francesca Maria Rossi
3,
Riccardo Bomben
3,
Antonella Zucchetto
3,
Valter Gattei
3,
Agostino Tafuri
1,‡ and
Maria Rosaria Ricciardi
1,*,‡
1
Hematology, Department of Clinical and Molecular Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, 00189 Rome, Italy
2
WS Audiology, 91058 Erlangen, Germany
3
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., 33081 Aviano, Italy
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
These authors contributed equally to this work.
Curr. Issues Mol. Biol. 2024, 46(6), 5085-5099; https://doi.org/10.3390/cimb46060305
Submission received: 21 March 2024 / Revised: 14 May 2024 / Accepted: 16 May 2024 / Published: 22 May 2024
(This article belongs to the Special Issue Advances in Pharmacotherapeutic Strategies to Prevent Tumor Development, Progression and Treatment Resistance)
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Abstract

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.
Keywords: bioenergetic metabolism; Chronic Lymphocytic Leukemia; BTK inhibition bioenergetic metabolism; Chronic Lymphocytic Leukemia; BTK inhibition

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MDPI and ACS Style

Mirabilii, S.; Piedimonte, M.; Conte, E.; Mirabilii, D.; Rossi, F.M.; Bomben, R.; Zucchetto, A.; Gattei, V.; Tafuri, A.; Ricciardi, M.R. Low Cell Bioenergetic Metabolism Characterizes Chronic Lymphocytic Leukemia Patients with Unfavorable Genetic Factors and with a Better Response to BTK Inhibition. Curr. Issues Mol. Biol. 2024, 46, 5085-5099. https://doi.org/10.3390/cimb46060305

AMA Style

Mirabilii S, Piedimonte M, Conte E, Mirabilii D, Rossi FM, Bomben R, Zucchetto A, Gattei V, Tafuri A, Ricciardi MR. Low Cell Bioenergetic Metabolism Characterizes Chronic Lymphocytic Leukemia Patients with Unfavorable Genetic Factors and with a Better Response to BTK Inhibition. Current Issues in Molecular Biology. 2024; 46(6):5085-5099. https://doi.org/10.3390/cimb46060305

Chicago/Turabian Style

Mirabilii, Simone, Monica Piedimonte, Esmeralda Conte, Daniele Mirabilii, Francesca Maria Rossi, Riccardo Bomben, Antonella Zucchetto, Valter Gattei, Agostino Tafuri, and Maria Rosaria Ricciardi. 2024. "Low Cell Bioenergetic Metabolism Characterizes Chronic Lymphocytic Leukemia Patients with Unfavorable Genetic Factors and with a Better Response to BTK Inhibition" Current Issues in Molecular Biology 46, no. 6: 5085-5099. https://doi.org/10.3390/cimb46060305

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