Identification of a novel resistance mechanism in venetoclax treatment and its prediction in chronic lymphocytic leukemia

Takács, Ferenc; Mikala, Gábor; Nagy, Noémi; Reszegi, Andrea; Czeti, Ágnes; Szalóki, Gábor; Barna, Gábor

doi:10.1080/0284186x.2021.1878388

Cited by 8 publications

(11 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Severity rating: less than 8 points, no depression, more than 20 points, and mild or moderate depression; a total score of more than 35 is considered severe depression. The reliability α coefficient of the scale is 0.90, indicating it is with good reliability and validity [ 18 , 19 ].…”

Section: The Mechanism and Effect Of Repetitive Transcranial Magnetic...mentioning

confidence: 99%

Cortical Plasticity Mechanism and Efficacy Prediction of Repeated Transcranial Magnetic Stimulation in the Treatment of Depression with Continuous Short Bursts of Rapid Pulse Stimulation (cTBS)

Hou¹,

Chen²,

Zhu³

et al. 2022

Mediators of Inflammation

View full text Add to dashboard Cite

In order to further explore the therapeutic effects of high-frequency and low-frequency repetitive transcranial magnetic stimulation on depression and cognitive function in the elderly, this paper proposed a study on cortical plasticity mechanism and efficacy prediction of repetitive transcranial magnetic stimulation based on continuous short pulse fast pulse stimulation (CTBS). This paper selected 92 patients with depression in a hospital from January to December 2020 as the research object and divided them into control group, low-frequency group, and high-frequency group, 31 cases, 29 cases, and 32 cases, respectively. The continuous short pulse rapid pulse stimulation (CTBS) mode was used to explore the effect of brain network on patients’ emotional processing. After clinical treatment contrast, there was no significant difference in HAMD-24 scores and RBANS scores before treatment ( P > 0.05 ), and there was a significant negative correlation between factors of cognitive impairment in patients and RBANS scores ( P < 0.01 or P < 0.05 ), so it was proved that the repeated transcranial magnetic stimulation (cTBS) could be used as an effective treatment for depression.

show abstract

Section: The Mechanism and Effect Of Repetitive Transcranial Magnetic...mentioning

confidence: 99%

Cortical Plasticity Mechanism and Efficacy Prediction of Repeated Transcranial Magnetic Stimulation in the Treatment of Depression with Continuous Short Bursts of Rapid Pulse Stimulation (cTBS)

Hou¹,

Chen²,

Zhu³

et al. 2022

Mediators of Inflammation

View full text Add to dashboard Cite

show abstract

“…Therefore, we had to establish a novel gating strategy using internal controls to calculate the median uorescence intensity value (MFI). This novel approach to measure MFI was based on our previously published work [23]. According to our measurements, the CD19 negative lymphocyte population was suitable as an internal negative control for CD69, CD184, CD185, and CD86.…”

Section: Flow Cytometrymentioning

confidence: 97%

Detection of Emerging Ibrutinib Resistance by Flow Cytometry in Patients with Chronic Lymphocytic Leukaemia

Takács

Kotmayer

Czeti

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Although ibrutinib is effective drug in the treatment of chronic lymphocytic leukaemia (CLL), during the treatment acquired resistance may occur, making its detection an important issue. We aimed to find phenotypic markers on CLL cells which expression may correlate with the appearance of ibrutinib resistance. Methods: We examined 28 (treatment naïve, ibrutinib sensitive, clinically ibrutinib resistant) peripheral blood (PB) samples. The surface markers` expression (CD69, CD184, CD86, CD185, CD27) were assessed by flow cytometry. Furthermore, the BTKC481S resistance mutation was tested using digital droplet PCR. We also investigated the change of the phenotype of CLL cells during ibrutinib treatment in one patient with acquired ibrutinib resistance. Results: The expression of CD27 (p=0.016), CD69 (p=0.015) and CD86 (p=0.015) was higher in the clinically resistant cohort than in the ibrutinib sensitive cohort. Besides, we found that high CD86 and CD27 expressions accompanied by BTKC481S mutation. Our prospective study showed that the increase of the expression of CD27, CD69, and CD86 was ahead of clinical resistance with three months. Conclusion: Our study suggests that the flow cytometric measurements of certain markers may reveal and predict the development of ibrutinib resistance, and this method may in the future become a part of the follow-up on patients treated with ibrutinib.

show abstract

“…The method used to measure median uorescence intensity (MFI) is based on our previously published work [21]. According to our measurements the CD19 negative lymphocyte population was suitable as an internal negative control for CD69, CD184, CD185 and CD86.…”

Section: Flow Cytometrymentioning

confidence: 99%

“…We determined the expression of CD27, CD69 and CD86 on days 0, 30, 90, 120, 240, 330 and on the onset of the clinical resistance (day 420). Clinical parameters of this patient were published previously [21]. Patients were informed in writing and written consent was obtained from all participants.…”

Section: Patients and Samplesmentioning

confidence: 99%

Detection of emerging ibrutinib resistance by flow cytometry in patients with chronic lymphocytic leukemia

Takács

Kotmayer

Czeti

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Bruton ’ s tyrosine kinase inhibitor ibrutinib has revolutionized the treatment of chronic lymphocytic leukemia (CLL). Although ibrutinib is a highly effective drug, continuous treatment is required to maintain remission, which may lead to acquired ibrutinib resistance. Early detection of acquired resistance preceding clinical disease progression is an important issue. This is why our aim was to investigate several phenotypic markers on CLL cells to reveal changes in their expression during ibrutinib treatment in sensitive and clinically resistant patients. Materials and methods: In our study 28 (treatment naive, ibrutinib sensitive, clinically ibrutinib resistant) peripheral blood (PB), and 6 paired PB and bone marrow (BM) samples from CLL patients were examined. The expression of several surface markers (CD69, CD184, CD86, CD185, CD27) was assessed by flow cytometry in each sample. Furthermore, the presence of the BTK C481S resistance mutation was tested using digital droplet PCR (ddPCR) in samples from ibrutinib sensitive and resistant cases. In addition, we investigated the changes of CLL cells ’ phenotype during ibrutinib treatment in one patient with acquired ibrutinib resistance. Results: We found that the expression of CD27 decreased during ibrutinib therapy but increased again at the onset of clinical resistance. Expressions of CD69 and CD86 were also elevated at the onset of clinical ibrutinib resistance. Furthermore, the expression of CD86 showed correlation between PB and BM samples. Relapsed cases with high CD86 expression were positive for BTK C481S mutation. In addition, our prospective study showed that the increases in the expression of CD27, CD69 and CD86 were detectable up to several months before the onset of clinical resistance. Conclusion: Our research suggests that the flow cytometric measurements of certain markers, especially CD86, may predict development of ibrutinib resistance, however, confirmatory experiments are still required. Monitoring CD86 expression on peripheral blood CLL cells during ibrutinib treatment may become a potential new method to detect acquired ibrutinib resistance in the near future.

show abstract

Identification of a novel resistance mechanism in venetoclax treatment and its prediction in chronic lymphocytic leukemia

Cited by 8 publications

References 16 publications

Cortical Plasticity Mechanism and Efficacy Prediction of Repeated Transcranial Magnetic Stimulation in the Treatment of Depression with Continuous Short Bursts of Rapid Pulse Stimulation (cTBS)

Cortical Plasticity Mechanism and Efficacy Prediction of Repeated Transcranial Magnetic Stimulation in the Treatment of Depression with Continuous Short Bursts of Rapid Pulse Stimulation (cTBS)

Detection of Emerging Ibrutinib Resistance by Flow Cytometry in Patients with Chronic Lymphocytic Leukaemia

Detection of emerging ibrutinib resistance by flow cytometry in patients with chronic lymphocytic leukemia

Contact Info

Product

Resources

About