Can Galectin-3 Be a Novel Biomarker in Chronic Lymphocytic Leukemia?
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Material and Patients’ Characteristics
2.2. Flow Cytometry Assessment
2.2.1. PBMCs Isolation
2.2.2. Cell Surface and Intracellular Stainings
2.3. Confocal Microscopy
2.4. Quantitative Measurement of Gal-3 mRNA Expression
2.4.1. Magnetic Isolation of CD19+ Cells
2.4.2. RT-qPCR
2.5. Gal-3 Detection in Plasma
2.6. Fluorescent In Situ Hybridization (FISH)
2.7. Statistical Analysis
3. Results
3.1. Heterogenous Gal-3 Expression in CLL Patients
3.2. The Relationship between the Molecular Profile of Patients and Gal-3 Levels
3.3. Assessment of the Influence of Gal-3 Expression on the Clinical Outcomes
3.4. The Relationship between the Level of mRNA Expression of Gal-3 and Bcl-2 and Proliferation Markers (Ki-67 and PCNA)
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | CLL Patients (n = 146) | HV (n = 26) |
---|---|---|
Gender | ||
Female, n (%) | 71 (48.6) | 12 (46.2) |
Male, n (%) | 75 (51.4) | 14 (56.8) |
Age (years) | ||
Median (IQR) | 66 (59–72) | 58 (53–62) |
Min–max | 37–88 | 35–64 |
Rai Stage [24] | ||
0, n (%) | 63 (43.2) | |
I, n (%) | 31 (21.2) | |
II, n (%) | 25 (17.1) | |
III, n (%) | 16 (11.0) | |
IV, n (%) | 11 (7.5) | |
ZAP-70-positive, n (%) * | 52 (35.6) | |
CD38-positive, n (%) * | 54 (37.0) | |
IGHV mutational status | ||
U-IGHV, n (%) | 22 (15.1) | |
M-IGHV, n (%) | 28 (19.2) | |
not available, n (%) | 96 (65.7) | |
Chromosomal aberrations | ||
17p-, n (%) | 12 (8.2) | |
11q-, n (%) | 13 (8.9) | |
+12, n (%) | 5 (3.4) | |
sole 13q-, n (%) | 40 (27.4) | |
Patients treated during observation period, n (%) # | 58 (39.7) | |
Complete remission (CR), n (%) | 12/58 (20.7) | |
Partial remission (PR), n (%) | 28/58 (48.3) | |
Stable disease (SD), n (%) | 13/58 (22.4) | |
Disease progression (PD), n (%) | 5/58 (8.6) | |
First line therapy | ||
fludarabine + cyclophosphamide + rituximab | 10/58 | |
bendamustine + rituximab | 15/58 | |
chlorambucil and obinutuzumab | 14/58 | |
rituximab + cyclophosphamide + deksametazon | 4/58 | |
venetoklax and obinutuzumab | 8/58 | |
ibrutinib | 4/58 | |
acalabrutinib | 3/58 | |
WBC (G/L), median (IQR) | 24.63 (17.2–55.16) | |
Lymphocyte count (G/L), median (IQR) | 18.32 (10.87–47.58) | |
LDH level (IU/L), median (IQR) | 349 (285–412) | |
β2M level (mg/dL), median (IQR) | 2.60 (2.08–3.40) |
Univariate Analysis | Multivariate Analysis | |||||
---|---|---|---|---|---|---|
Risk Factors | HR | 95% CI | p-Value | HR | 95% CI | p-Value |
High ZAP-70 expression | 1.803 | 1.240–2.620 | 0.002 | 1.676 | 0.797–3.527 | 0.173 |
High CD38 expression | 1.339 | 0.908–1.975 | 0.140 | na | ||
High β2M level | 2.437 | 1.631–3.643 | <0.0001 | 2.319 | 1.103–4.875 | 0.026 |
Positive 17p− and/or 11q− | 2.480 | 1.372–4.614 | <0.001 | 3.038 | 1.343–6.871 | 0.007 |
High Gal-3 mRNA level | 2.123 | 1.172–3.846 | 0.013 | 2.492 | 0.706–8.793 | 0.155 |
High percentage of Gal-3-positive B cells | 2.226 | 1.164–4.259 | 0.015 | 0.696 | 0.220–2.205 | 0.538 |
High Gal-3 plasma level | 1.037 | 0.634–1.698 | 0.886 | na |
Membrane Gal-3 (%) | Intracellular Gal-3 (%) | Gal-3 mRNA (2−ΔCq) | ||||
---|---|---|---|---|---|---|
Patient No. | At the Time of Diagnosis | After Treatment | At the Time of Diagnosis | After Treatment | At the Time of Diagnosis | After Treatment |
1. | 2.89 | 2.86 | 2.59 | 3.39 | 1.75 | 3.78 |
2. | 6.93 | 4.56 | 18.86 | 14.16 | 5.32 | 4.32 |
3. | 8.96 | 5.41 | 7.66 | 6.02 | 3.80 | 3.63 |
4. | 2.5 | 2.53 | 21.6 | 26.26 | 5.21 | 6.5 |
5. | 4.1 | 8.06 | 23.75 | 26.34 | 2.58 | 3.22 |
6. | 6.89 | 3.88 | 22.01 | 8.75 | 3.88 | 3.09 |
7. | 3.02 | 4.02 | 9.89 | 11.82 | 3.21 | 4.58 |
8. | 5.57 | 4.56 | 8.36 | 6.73 | 4.64 | 3.66 |
Median | 4.835 * | 4.29 * | 14.38 # | 10.29 # | 3.84 ^ | 3.72 ^ |
IQR | 2.92–6.92 | 3.12–5.19 | 7.83–21.91 | 6.19–23.24 | 2.74–5.07 | 3.32–4.51 |
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Woś, J.; Szymańska, A.; Lehman, N.; Chocholska, S.; Zarobkiewicz, M.; Pożarowski, P.; Bojarska-Junak, A. Can Galectin-3 Be a Novel Biomarker in Chronic Lymphocytic Leukemia? Cells 2024, 13, 30. https://doi.org/10.3390/cells13010030
Woś J, Szymańska A, Lehman N, Chocholska S, Zarobkiewicz M, Pożarowski P, Bojarska-Junak A. Can Galectin-3 Be a Novel Biomarker in Chronic Lymphocytic Leukemia? Cells. 2024; 13(1):30. https://doi.org/10.3390/cells13010030
Chicago/Turabian StyleWoś, Justyna, Agata Szymańska, Natalia Lehman, Sylwia Chocholska, Michał Zarobkiewicz, Piotr Pożarowski, and Agnieszka Bojarska-Junak. 2024. "Can Galectin-3 Be a Novel Biomarker in Chronic Lymphocytic Leukemia?" Cells 13, no. 1: 30. https://doi.org/10.3390/cells13010030
APA StyleWoś, J., Szymańska, A., Lehman, N., Chocholska, S., Zarobkiewicz, M., Pożarowski, P., & Bojarska-Junak, A. (2024). Can Galectin-3 Be a Novel Biomarker in Chronic Lymphocytic Leukemia? Cells, 13(1), 30. https://doi.org/10.3390/cells13010030