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. 2025 Oct 14;9(19):4891-4895.
doi: 10.1182/bloodadvances.2024014977.

Ibrutinib increases miR-181a/b in leukemic cells from patients with chronic lymphocytic leukemia

Alice Ramassone  1   2 , Sara Pagotto  1   2 , Mirco Di Marco  2 , Mohammad Mamunur Rashid  2 , Carola Di Camillo  1   2 , Fabiana Palmiero  2 , Idanna Innocenti  3 , Francesco Autore  3 , Annamaria Tomasso  3 , Luca Laurenti  3 , Rosa Visone  1   2   4
Affiliations

Ibrutinib increases miR-181a/b in leukemic cells from patients with chronic lymphocytic leukemia

Alice Ramassone et al. Blood Adv. .
No abstract available

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Conflict of interest statement

Conflict-of-interest disclosure: L.L. reports advisory roles for AstraZeneca, Johnson & Johnson, BeiGene, AbbVie, and Lilly during the preparation of the manuscript. The remaining authors declare no competing financial interests.

The current affiliation for M.M.R. is Albert Einstein College of Medicine, Bronx, NY.

The current affiliation for F.P. is Max von Pettenkofer-Institut, Ludwig-Maximilians-Universität, München, Germany.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Ibrutinib affects miR-181a and miR-181b expression in vivo. (A) Evaluation by reverse transcription quantitative polymerase chain reaction (RT-qPCR) of miR-181a and miR-181b relative expression in purified primary CLL cells collected at the first time point (FTP) and at the last time point (LTP) of ibrutinib treatment follow-up. RNU44 was used as an internal control. The expression of miRNAs was normalized to the level of the basal time point at each time point. The Wilcoxon matched-pairs test was used for statistical significance. (B) Evaluation by RT-qPCR of miR-181a and miR-181b expression (left y-axis) in purified primary CLL cells collected during the follow-up of ibrutinib treatment (x-axis; days); RNU44 was used as an internal control. The expression of miRNAs was normalized to the level of the basal time point at each time point. WBC count at each time point was reported on the right y-axis. Black arrows indicate when the WBC count of patients decreased by >50% from baseline, or reached physiologic values at the last time point (WBC with properties). Conversely, gray arrows represent time points where the WBC count of patients decreased by <50% from baseline or remained unchanged (WBC without properties). (C) Graphs illustrate the corresponding expression levels of miR-181a and miR-181b in patients with CLL, as indicated. Wilcoxon matched-pairs test was used for statistical significance; ∗P<.05.
Figure 2.
Figure 2.
miR-181a and miR-181b expression increases after ibrutinib treatment in patients with CLL in vitro. The relative expression of miR-181a (A) and miR-181b (B) was evaluated by RT-qPCR in purified primary CLL cells treated for 72 hours with ibrutinib 10 μM, or DMSO as a control. RNU44 was used as an internal control. The relative expression of miRNAs for each patient was normalized to the DMSO-treated sample. miR-181a expression was assessed in 28 patients with CLL, with 21 analyzed in experimental duplicates and 7 (CLL45B, CLL176, CLL192, CLL197, CLL198, CLL210, and CLL211) analyzed in a single experiment. Similarly, miR-181b expression was evaluated in 27 patients with CLL, with 24 analyzed in duplicates and 3 (CLL161, CLL176, and CLL198) in a single experiment. The Wilcoxon matched-pairs test was used for statistical significance. (C) Cell viability of purified primary CLL cells was assessed after treatment with increasing doses of ibrutinib or DMSO (0, 10, and 100 μM) for 72 hours using the MTS (3-(4,5 dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl)-2H-tetrazolium)) assay. Statistical significance was determined by 1-way analysis of variance (ANOVA). (D) Cell viability of primary CLL cells transfected with either pTween_181b, pTween_181a, or pTween_CTRL vectors was evaluated after a 72-hour treatment with increasing concentrations of ibrutinib or DMSO (0, 10, and 100 μM). Cell viability was determined using the MTS assay. Statistical significance was assessed by 1-way ANOVA. DMSO, dimethyl sulfoxide.
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