Unmutated IGHV1-69 CLL Clone Displays a Distinct Gene Expression Profile by a Comparative qRT-PCR Assay
Chronic Lymphocytic Leukemia (CLL) is a heterogeneous disease characterized by variable clinical courses among different patients. This notion was supported by the possible coexistence of two or more independent CLL clones within the same patients, identified by the characterization of the B cell re...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-03-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/10/3/604 |
| _version_ | 1827649895497990144 |
|---|---|
| author | Selena Mimmi Domenico Maisano Vincenzo Dattilo Massimo Gentile Federico Chiurazzi Alessandro D’Ambrosio Annamaria Zimbo Nancy Nisticò Annamaria Aloisio Eleonora Vecchio Giuseppe Fiume Enrico Iaccino Ileana Quinto |
| author_facet | Selena Mimmi Domenico Maisano Vincenzo Dattilo Massimo Gentile Federico Chiurazzi Alessandro D’Ambrosio Annamaria Zimbo Nancy Nisticò Annamaria Aloisio Eleonora Vecchio Giuseppe Fiume Enrico Iaccino Ileana Quinto |
| author_sort | Selena Mimmi |
| collection | DOAJ |
| description | Chronic Lymphocytic Leukemia (CLL) is a heterogeneous disease characterized by variable clinical courses among different patients. This notion was supported by the possible coexistence of two or more independent CLL clones within the same patients, identified by the characterization of the B cell receptor immunoglobulin (BcR IG) idiotypic sequence. By using the antigen-binding site of the BcR IG as bait, the identification and isolation of aggressive and drug-resistance leukemic B-cell clones could allow a deeper biological and molecular investigation. Indeed, by the screening of phage display libraries, we previously selected a peptide binder of the idiotypic region of CLL BCR IGs expressing the unmutated rearrangement IGHV1-69 and used it as a probe to perform a peptide-based cell sorting by flow cytometry in peripheral blood samples from patients with CLL. Since the IGHV1-69 clones persisted during the follow-up time in both patients, we explored the possibility of these clones having acquired an evolutive advantage compared to the other coexisting clones in terms of a higher expression of genes involved in the survival and apoptosis escape processes. To this end, we studied the expression patterns of a panel of genes involved in apoptosis regulation and in NF-kB-dependent pro-survival signals by comparative qRT-PCR assays. According to the results, IGHV1-69 clones showed a higher expression of pro-survival and anti-apoptotic genes as compared to the other CLL clones with different immunogenetic characteristics. Moreover, these IGHV1-69 clones did not carry any characteristic genetic lesions, indicating the relevance of our approach in performing a comprehensive molecular characterization of single tumor clones, as well as for designing new personalized therapeutic approaches for the most aggressive and persistent tumor clones. |
| first_indexed | 2024-03-09T20:05:59Z |
| format | Article |
| id | doaj.art-97bf20c8ef20425f993dfd604efbd2ee |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T20:05:59Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-97bf20c8ef20425f993dfd604efbd2ee2023-11-24T00:32:39ZengMDPI AGBiomedicines2227-90592022-03-0110360410.3390/biomedicines10030604Unmutated IGHV1-69 CLL Clone Displays a Distinct Gene Expression Profile by a Comparative qRT-PCR AssaySelena Mimmi0Domenico Maisano1Vincenzo Dattilo2Massimo Gentile3Federico Chiurazzi4Alessandro D’Ambrosio5Annamaria Zimbo6Nancy Nisticò7Annamaria Aloisio8Eleonora Vecchio9Giuseppe Fiume10Enrico Iaccino11Ileana Quinto12Laboratory of Immunology, Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyLaboratory of Immunology, Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyLaboratory Genetics Unit, IRCCS Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, ItalyHematology Unit, Department of Onco-Hematology, A.O of Cosenza, 87100 Cosenza, ItalyHematological Clinic, Department of Clinical Medicine, University of Naples Federico II, 80131 Naples, ItalyHematological Clinic, Department of Clinical Medicine, University of Naples Federico II, 80131 Naples, ItalyLaboratory of Immunology, Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyLaboratory of Immunology, Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyLaboratory of Immunology, Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyLaboratory of Immunology, Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyLaboratory of Immunology, Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyLaboratory of Immunology, Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyLaboratory of Immunology, Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyChronic Lymphocytic Leukemia (CLL) is a heterogeneous disease characterized by variable clinical courses among different patients. This notion was supported by the possible coexistence of two or more independent CLL clones within the same patients, identified by the characterization of the B cell receptor immunoglobulin (BcR IG) idiotypic sequence. By using the antigen-binding site of the BcR IG as bait, the identification and isolation of aggressive and drug-resistance leukemic B-cell clones could allow a deeper biological and molecular investigation. Indeed, by the screening of phage display libraries, we previously selected a peptide binder of the idiotypic region of CLL BCR IGs expressing the unmutated rearrangement IGHV1-69 and used it as a probe to perform a peptide-based cell sorting by flow cytometry in peripheral blood samples from patients with CLL. Since the IGHV1-69 clones persisted during the follow-up time in both patients, we explored the possibility of these clones having acquired an evolutive advantage compared to the other coexisting clones in terms of a higher expression of genes involved in the survival and apoptosis escape processes. To this end, we studied the expression patterns of a panel of genes involved in apoptosis regulation and in NF-kB-dependent pro-survival signals by comparative qRT-PCR assays. According to the results, IGHV1-69 clones showed a higher expression of pro-survival and anti-apoptotic genes as compared to the other CLL clones with different immunogenetic characteristics. Moreover, these IGHV1-69 clones did not carry any characteristic genetic lesions, indicating the relevance of our approach in performing a comprehensive molecular characterization of single tumor clones, as well as for designing new personalized therapeutic approaches for the most aggressive and persistent tumor clones.https://www.mdpi.com/2227-9059/10/3/604B-cellschronic lymphocytic leukemiagene expression analysisCLL heterogeneityB-lymphoproliferative disordersphage display |
| spellingShingle | Selena Mimmi Domenico Maisano Vincenzo Dattilo Massimo Gentile Federico Chiurazzi Alessandro D’Ambrosio Annamaria Zimbo Nancy Nisticò Annamaria Aloisio Eleonora Vecchio Giuseppe Fiume Enrico Iaccino Ileana Quinto Unmutated IGHV1-69 CLL Clone Displays a Distinct Gene Expression Profile by a Comparative qRT-PCR Assay Biomedicines B-cells chronic lymphocytic leukemia gene expression analysis CLL heterogeneity B-lymphoproliferative disorders phage display |
| title | Unmutated IGHV1-69 CLL Clone Displays a Distinct Gene Expression Profile by a Comparative qRT-PCR Assay |
| title_full | Unmutated IGHV1-69 CLL Clone Displays a Distinct Gene Expression Profile by a Comparative qRT-PCR Assay |
| title_fullStr | Unmutated IGHV1-69 CLL Clone Displays a Distinct Gene Expression Profile by a Comparative qRT-PCR Assay |
| title_full_unstemmed | Unmutated IGHV1-69 CLL Clone Displays a Distinct Gene Expression Profile by a Comparative qRT-PCR Assay |
| title_short | Unmutated IGHV1-69 CLL Clone Displays a Distinct Gene Expression Profile by a Comparative qRT-PCR Assay |
| title_sort | unmutated ighv1 69 cll clone displays a distinct gene expression profile by a comparative qrt pcr assay |
| topic | B-cells chronic lymphocytic leukemia gene expression analysis CLL heterogeneity B-lymphoproliferative disorders phage display |
| url | https://www.mdpi.com/2227-9059/10/3/604 |
| work_keys_str_mv | AT selenamimmi unmutatedighv169cllclonedisplaysadistinctgeneexpressionprofilebyacomparativeqrtpcrassay AT domenicomaisano unmutatedighv169cllclonedisplaysadistinctgeneexpressionprofilebyacomparativeqrtpcrassay AT vincenzodattilo unmutatedighv169cllclonedisplaysadistinctgeneexpressionprofilebyacomparativeqrtpcrassay AT massimogentile unmutatedighv169cllclonedisplaysadistinctgeneexpressionprofilebyacomparativeqrtpcrassay AT federicochiurazzi unmutatedighv169cllclonedisplaysadistinctgeneexpressionprofilebyacomparativeqrtpcrassay AT alessandrodambrosio unmutatedighv169cllclonedisplaysadistinctgeneexpressionprofilebyacomparativeqrtpcrassay AT annamariazimbo unmutatedighv169cllclonedisplaysadistinctgeneexpressionprofilebyacomparativeqrtpcrassay AT nancynistico unmutatedighv169cllclonedisplaysadistinctgeneexpressionprofilebyacomparativeqrtpcrassay AT annamariaaloisio unmutatedighv169cllclonedisplaysadistinctgeneexpressionprofilebyacomparativeqrtpcrassay AT eleonoravecchio unmutatedighv169cllclonedisplaysadistinctgeneexpressionprofilebyacomparativeqrtpcrassay AT giuseppefiume unmutatedighv169cllclonedisplaysadistinctgeneexpressionprofilebyacomparativeqrtpcrassay AT enricoiaccino unmutatedighv169cllclonedisplaysadistinctgeneexpressionprofilebyacomparativeqrtpcrassay AT ileanaquinto unmutatedighv169cllclonedisplaysadistinctgeneexpressionprofilebyacomparativeqrtpcrassay |