Roles and Regulation of BCL-xL in Hematological Malignancies
Abstract
:1. Introduction
2. BCL-xL in Hematological Malignancies
2.1. BCL-xL in Non-Hodgkin Lymphoma
2.2. BCL-xL in Leukemia
2.3. BCL-xL in Multiple Myeloma
3. Regulation of BCL-xL
3.1. BCL-xL Regulation by Transcription Factors
3.2. MicroRNAs and BCL-xL
3.3. LeukemiRs and LymphomiRs in the Regulation of BCL-xL
3.4. BCL-XL as a Potential Biomarker in Hematological Malignancies
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
B-ALL | B-cell Acute lymphocytic leukemia |
B-NHL | B non-Hodgkin lymphoma |
DLBCL | diffuse large B cell lymphoma |
FL | Follicular Lymphoma |
IHC | immunohistochemistry |
IPI | International prognostic index |
MGUS | Monoclonal gammopathy of undetermined significance |
MM | Multiple Myeloma |
MZBCL | marginal zone b-cell lymphoma |
SM | Smoldering Myeloma |
T-ALL | T-cell Acute lymphocytic leukemia |
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Transcription Factor | Potential Sites |
---|---|
ARNT::HIF1A | −62, −377, −532, −842 |
ASCL1 | −16, −17, −112, −342, −383, −522, −523, −628, −835, −867 |
Ahr::Arnt | −62, −842 |
Ar | −96, −670, −856 |
Arnt | −377, −532 |
Arntl | −377 |
Ascl2 | −166, −383, −523 |
Atoh1 | −337 |
BACH2 | 63, −262 |
BCL6B | −353, −362, −540 |
Bcl6 | −542, −734 |
CLOCK | −337, −376, −377, −532, −533 |
CTCF | 70, −36, −83, −112, −293, −336, −574, −577, −645, −705, −710, −753 |
E2F1 | −435, −568, −569, −715, −716, −944 |
EGR1 | 34, −49, −506, −799 |
ELF1 | 60, 22, −37, −488, −538, −799 |
FOXA1 | −124 |
HSF1 | −922 |
IRF1 | −140 |
KLF4 | −64, −175, −459, −619, −898 |
KLF14 | 37, −22, −46, −64, −79, −294, −602, −681, −714, −717, −738, −749, −763, −827, −854 |
MYC | −376, −533 |
SP1 | 20, −45, −78, −181, −247, −285, −412, −460, −492, −591, −620, −681, −704, −739, −748, −762, −803, −855 |
YY1 | −425 |
Hematological Malignancies | miRNAs Related |
---|---|
B-Cell Lymphoma | miR-17-92, miR-34a, miR-21. |
DLBCL | miR-155, miR-125, |
FL | miR-17-92, |
AML | miR-155, miR-125, miR-181, miR-221/222, miR-29a, miR-124a. |
ALL | miR-17-92, miR-125, miR-15a/16-1, miR-124a. |
CLL | miR-181, miR-221/222, miR-29a, miR-15a/16-1. |
CML | miR-17-92, |
MM | miR-17-92, miR-15a/16-1, miR-21 |
LeukermiRs | Leukemia Type | Expression | Role |
---|---|---|---|
miR-511, miR-222, miR-34 | ALL | High | Leukemogenesis |
miR-199a-3p, miR-223, miR-221, miR-26a. | ALL | Down | Leukemogenesis |
miR-181b-5p, miR-181a-3p, miR-181a-5p, miR-342-3p | -- | Dysregulated | Differentiate subtypes of leukemia. |
miR-450a-5p, miR-1225a, | -- | Dysregulated | Dysregulated in all subtypes of leukemia |
miR-128, miR-146a, miR-155, miR-181a, miR-195 | ALL | High | High expression vs. healthy control. |
Let-7, miR-223 | ALL | Lower | Lower expression in ALL vs. AML |
miR-29c-5p | ALL | High | Increased expression allows one to difference between B and T ALL. |
LymphomiR | Target | Roll | Refs. |
---|---|---|---|
miR-34 | FOXP3, SIRT1 | Media transition pro-B a pre-B | [70] |
miR-7 | KLF4, YY1 | Chemoresistance & migration | [61] |
miR-17-5p | E2F1 | Cell Cycle Regulation | [71] |
miR-106b | P21/CDK1 | Cell Cycle Regulation | [72] |
miR-17-92 cluster | HIF-1a | Chemoresistance | [73] |
miR-155 | TP53INP | Tumor growth | [74] |
Upregulated in DLBCL by small-RNA-seq [65] | Downregulated in DLBCL by small-RNA-seq [65] | Downregulated in DLBCL and BL [41] | Upregulated in FL [63] | Downregulated in FL [63] | ||
---|---|---|---|---|---|---|
miR-124 | miR-425 | miR-150 | miR-193a-5p | miR-1295 | miR-17 * | miR-222 |
miR-532-5p | miR-141 | miR-189 | miR-193b * | miR-1471 | miR-30a | miR-301b |
miR-145 | miR-223 | miR-345 | miR-33a | miR-431 * | ||
miR-197 | miR-768-3p | miR-513b | miR-106a * | |||
miR-345 | miR-15 | miR-574-3p | miR-141 | |||
miR-424 | miR-584 | miR-202 | ||||
miR-128 | miR-663 | miR-205 | ||||
miR-122 | miR-1287 | miR-570 |
Target and microRNA | Position |
---|---|
Position 85–92 of BCL2L1 3’ UTR hsa-miR-140-5p | 5’ ...CAUUGCCACCAGGAG--AACCACUA... ||| ||||||| 3’ GAUGGUAUCCCAUUUUGGUGAC |
Position 88–94 of BCL2L1 3’ UTR hsa-miR-142-3p.1 | 5’ ...UGCCACCAGGAGAACCACUACAU... ||||||| 3’ AGGUAUUUCAUCCUUUGUGAUGU |
Position 764–771 of BCL2L1 3’ UTR hsa-miR-133a-3p.1 | 5’ ...CCAUGACCAUACUGAGGGACCAA... ||||||| 3’ GUCGACCAACUUCCCCUGGUU |
Position 765–771 of BCL2L1 3’ UTR hsa-miR-133a-3p.2 | 5’ ...CAUGACCAUACUGAGGGACCAAC... ||||||| 3’ GUCGACCAACUUCCCCUGGUUU |
Position 765–771 of BCL2L1 3’ UTR hsa-miR-133b | 5’ ...CAUGACCAUACUGAGGGACCAAC... ||||||| 3’ AUCGACCAACUUCCCCUGGUUU |
Position 938–944 of BCL2L1 3’ UTR hsa-miR-7-5p | 5’ ...UAUGGGAGCCCCAGGGUCUUCCC... ||||||| 3’ UGUUGUUUUAGUGAUCAGAAGGU |
Position 945–952 of BCL2L1 3’ UTR hsa-miR-4458 | 5’ ...GCCCCAGGGUCUUCC----CUACCUCA... |||||| ||||||| 3’ AAGAAGGUGUGGAUGGAGA |
Position 945–952 of BCL2L1 3’ UTR hsa-miR-4500 | 5’ ...GCCCCAGGGUCUUCCCUACCUCA... ||||||| 3’ UUCUUUGAUGAUGGAGU |
Position 945–952 of BCL2L1 3’ UTR hsa-let-7b-5p | 5’ ...GCCCCAGGGUCUUCCCUACCUCA... ||||||| 3’ UUGGUGUGUUGGAUGAUGGAGU |
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Morales-Martínez, M.; Vega, M.I. Roles and Regulation of BCL-xL in Hematological Malignancies. Int. J. Mol. Sci. 2022, 23, 2193. https://doi.org/10.3390/ijms23042193
Morales-Martínez M, Vega MI. Roles and Regulation of BCL-xL in Hematological Malignancies. International Journal of Molecular Sciences. 2022; 23(4):2193. https://doi.org/10.3390/ijms23042193
Chicago/Turabian StyleMorales-Martínez, Mario, and Mario I. Vega. 2022. "Roles and Regulation of BCL-xL in Hematological Malignancies" International Journal of Molecular Sciences 23, no. 4: 2193. https://doi.org/10.3390/ijms23042193
APA StyleMorales-Martínez, M., & Vega, M. I. (2022). Roles and Regulation of BCL-xL in Hematological Malignancies. International Journal of Molecular Sciences, 23(4), 2193. https://doi.org/10.3390/ijms23042193