Relation of Neutrophil Gelatinase-Associated Lipocalin Overexpression to the Resistance to Apoptosis of Tumor B Cells in Chronic Lymphocytic Leukemia
Abstract
:1. Introduction
2. Results
2.1. Serum NGAL Levels Are Elevated in Untreated Patients with CLL, and Return to Basal Levels When Patients Achieve Remission
2.2. The Expression of NGAL Reveals Differences between PBMCs from Normal Controls and Patients with CLL
2.3. NGAL-R Is Overexpressed in CLL Cells from Untreated Patients, and Downregulated in CLL Cells from Patients in Remission
2.4. Blocking NGAL-R Induces Death in NGAL-R+ CLL Cells
2.5. NGAL Protects CLL Cells from Spontaneous Death
2.6. NGAL Counteracts the Intrinsic Apoptosis Pathway in CLL Cells
2.7. NGAL Upregulates the Expression of Mcl-1 and STAT3 in CLL Cells
2.8. NGAL-Mediated CLL Cell Survival Involves the Src/STAT3/Mcl-1 Signaling Pathway
3. Discussion
4. Methods
4.1. Ethics Statement
4.2. Patients, Serum and Cell Separation
4.3. Cell Culture Conditions
4.4. ELISAs
4.5. Flow Cytometry
4.6. DNA Fragmentation Assay
4.7. Real Time PCR Assays
4.8. Immunoblotting
4.9. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Acknowledgments
Conflicts of Interest
References
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Patient | Sex/Age | Stage | IGHV Mutation | FISH | Karyotype | Therapy |
---|---|---|---|---|---|---|
1 | M/71 | A | M | Trisomy 12 | 1 abnormality | None |
2 | M/63 | A | ND | 13q- | Complex | None |
3 | M/90 | A | M | ND | ND | None |
4 | M/88 | A | M | 13q- | Normal | None |
5 | M/76 | A | ND | 13q- | Normal | None |
6 | M/87 | C | M | 17p-, 13q- | Normal | None |
7 | M/66 | B | M | 13q- | 2 abnormalities | None |
8 | M/71 | A | ND | 13q- | Normal | None |
9 | M/71 | A | M | 11q-, 13q- | 1 abnormality | None |
10 | F/69 | B | ND | 13q- | Normal | None |
11 | F/74 | A | UM | 13q- | Normal | None |
12 | F/74 | A | M | Normal | Normal | None |
13 | F/78 | A | M | 13q- | Normal | None |
14 | M/73 | A | M | Normal | Normal | None |
15 | F/68 | A | ND | 13q- | 1 abnormality | None |
16 | F/62 | B | UM | 13q- | Normal | None |
17 | F/69 | A | M | 13q- | Normal | None |
18 | F/87 | A | ND | 13q- | Normal | None |
19 | F/83 | A | ND | Normal | Normal | None |
20 | M/86 | A | ND | Normal | Normal | None |
21 | M/86 | A | M | Trisomy 12 | Complex | None |
22 | M/82 | A | ND | 11q-, 13q- | Normal | None |
23 | F/77 | A | UM | 13q- | Failure | None |
24 | M/74 | A | ND | 13q- | 2 abnormalities | None |
25 | M/86 | A | M | 13q- | ND | None |
26 | F/76 | A | UM | 11q-, 13q- | Normal | None |
27 | F/88 | A | ND | ND | ND | None |
28 | F/64 | A | M | 13q- | Normal | None |
29 | M/70 | A | ND | 13q- | Normal | None |
30 | M/75 | A | M | 13q- | Normal | None |
31 | F/67 | A | ND | 13q- | Normal | None |
32 | F/74 | A | ND | 13q- | 1 abnormality | None |
33 | M/76 | A | ND | 13q- | Normal | None |
34 | M/68 | B | ND | 11q- | Complex | None |
35 | F/85 | A | M | 13q- | Normal | None |
36 | F/70 | A | ND | 13q- | Normal | None |
37 | F/52 | A | ND | 13q- | Normal | None |
38 | F/79 | A | ND | 13q- | Normal | None |
39 | F/54 | B | ND | Trisomy 12 | 1 abnormality | None |
40 | M/76 | A | M | 13q- | Normal | None |
41 | F/57 | A | ND | 13q- | Normal | None |
42 | M/72 | A | M | 13q- | ND | None |
43 | F/84 | A | ND | Normal | Normal | None |
44 | F/80 | B | ND | 11q- | 1 abnormality | None |
45 | M/62 | A | ND | Normal | Normal | None |
46 | M/75 | B | UM | Trisomy 12 | 1 abnormality | None |
47 | F/73 | A | ND | 13q- | Failure | None |
48 | M/59 | A | ND | ND | ND | None |
49 | F/75 | A | ND | 13q- | Normal | None |
50 | M/61 | B | ND | 13q-, Trisomy 12 | Complex | None |
51 | F/82 | A | ND | 13q- | Normal | None |
52 | F/53 | A | UM | 13q- | 2 abnormalities | None |
53 | M/71 | A | UM | 11q-, 13q- | ND | None |
54 | F/96 | A | UM | Trisomy 12 | 1 abnormality | None |
55 | M/72 | A | ND | Normal | Normal | None |
56 | F/85 | A | ND | Normal | 2 abnormalities | None |
57 | F/69 | A | M | Normal | Normal | None |
58 | F/51 | B | UM | 11q-, 13q- | 1 abnormality | None |
59 | M/63 | B | UM | 13q- | Normal | None |
60 | M/70 | B | UM | 11q-, 13q- | 2 abnormalities | None |
61 | F/80 | B | ND | 11q- | 1 abnormality | Ibrutinib/relapse |
62 | M/62 | B | UM | 11q-, 13q- | 1 abnormality | FCR/relapse |
63 | F/78 | A | M | 13q- | 1 abnormality | RCb/relapse |
64 | M/54 | B | UM | 13q- | 2 abnormalities | Ibrutinib/remission |
65 | F/78 | C | UM | 17p-, 13q-, Trisomy 12 | Complex | Ibrutinib/remission |
66 | M/76 | B | ND | 17p-, 13q- | 2 abnormalities | Ibrutinib/relapse |
67 | M/80 | B | UM | 17p-, 13q- | Complex | Ibrutinib/relapse |
68 | M/54 | C | UM | 17p-, 11q- | Complex | Ibrutinib/remission |
69 | F/72 | B | UM | 17p-, Trisomy 12 | Complex | Ibrutinib/remission |
70 | M/92 | A | ND | ND | ND | Cb/relapse |
71 | M/66 | C | UM | 13q-, Trisomy 12 | Complex | Ibrutinib/remission |
72 | M/70 | A | M&UM | 11q- | Failure | FCR/relapse |
73 | F/77 | A | M | Normal | ND | FC/relapse |
74 | M/88 | C | UM | 17p-, Trisomy 12 | Normal | RCb/remission |
75 | M/82 | C | UM | 11q-, 13q- | Complex | BR/relapse |
76 | M/79 | B | UM | Normal | Normal | BR/remission |
77 | M/64 | A | UM | Trisomy 12 | 1 abnormality | FCR/cyclosporine/remission |
78 | F/75 | B | M | 13q-, Trisomy 12 | 1 abnormality | FCR/remission |
79 | F/84 | B | ND | Normal | Complex | Ibrutinib/remission |
80 | F/64 | B | UM | 13q- | Normal | FCR/remission |
81 | M/69 | B | ND | 11q- | Complex | FCR x4/remission |
82 | M/75 | B | M | Trisomy 12 | 1 abnormality | BR/remission |
83 | M/74 | C | M | 11q-, 13q- | ND | MiniCHOP/remission |
84 | M/81 | C | M | 11q-, 13q- | ND | Alemtuzumab/relapse |
85 | M/75 | B | UM | 17p-, 13q- | 2 abnormalities | FCR x2/relapse |
Patient P16/Months | Lymphocyte Count (G/L) | Neutrophil Count (G/L) |
0 | 159.6 | 12.55 |
5 | 179.86 | 26 |
7 | 189.38 | 12.91 |
9 | 196.14 | 2.13 |
11 | 239.94 | 4.0 |
12 | 248.5 | 5.29 |
19 (treated) | 0.26 | 0.80 |
27 (treated) | 0.59 | 2.28 |
Correlation with: | p-value | p-value |
serum NGAL | 0.0011 | 0.6191 |
serum CPX | 0.0011 | 0.6191 |
Patient P46/Months | Lymphocyte Count (G/L) | Neutrophil Count (G/L) |
0 | 146 | 1.5 |
1.5 | 184 | 3.9 |
4 | 219.5 | 2.3 |
10 (treated) | 1.11 | 4.39 |
Correlation with: | p-value | p-value |
serum NGAL | 0.0833 | 0.7500 |
serum CPX | 0.3333 | 0.3333 |
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Share and Cite
Bauvois, B.; Pramil, E.; Jondreville, L.; Chapiro, E.; Quiney, C.; Maloum, K.; Susin, S.A.; Nguyen-Khac, F. Relation of Neutrophil Gelatinase-Associated Lipocalin Overexpression to the Resistance to Apoptosis of Tumor B Cells in Chronic Lymphocytic Leukemia. Cancers 2020, 12, 2124. https://doi.org/10.3390/cancers12082124
Bauvois B, Pramil E, Jondreville L, Chapiro E, Quiney C, Maloum K, Susin SA, Nguyen-Khac F. Relation of Neutrophil Gelatinase-Associated Lipocalin Overexpression to the Resistance to Apoptosis of Tumor B Cells in Chronic Lymphocytic Leukemia. Cancers. 2020; 12(8):2124. https://doi.org/10.3390/cancers12082124
Chicago/Turabian StyleBauvois, Brigitte, Elodie Pramil, Ludovic Jondreville, Elise Chapiro, Claire Quiney, Karim Maloum, Santos A. Susin, and Florence Nguyen-Khac. 2020. "Relation of Neutrophil Gelatinase-Associated Lipocalin Overexpression to the Resistance to Apoptosis of Tumor B Cells in Chronic Lymphocytic Leukemia" Cancers 12, no. 8: 2124. https://doi.org/10.3390/cancers12082124