Analysis of Intratumoral Heterogeneity in Myelodysplastic Syndromes with Isolated del(5q) Using a Single Cell Approach
Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological diseases. Among them, the most well characterized subtype is MDS with isolated chromosome 5q deletion (MDS del(5q)), which is the only one defined by a cytogenetic abnormality that makes these patients candidates to be treate...
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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/4/841 |
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| author | Pamela Acha Laura Palomo Francisco Fuster-Tormo Blanca Xicoy Mar Mallo Ana Manzanares Javier Grau Silvia Marcé Isabel Granada Marta Rodríguez-Luaces María Diez-Campelo Lurdes Zamora Francesc Solé |
| author_facet | Pamela Acha Laura Palomo Francisco Fuster-Tormo Blanca Xicoy Mar Mallo Ana Manzanares Javier Grau Silvia Marcé Isabel Granada Marta Rodríguez-Luaces María Diez-Campelo Lurdes Zamora Francesc Solé |
| author_sort | Pamela Acha |
| collection | DOAJ |
| description | Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological diseases. Among them, the most well characterized subtype is MDS with isolated chromosome 5q deletion (MDS del(5q)), which is the only one defined by a cytogenetic abnormality that makes these patients candidates to be treated with lenalidomide. During the last decade, single cell (SC) analysis has emerged as a powerful tool to decipher clonal architecture and to further understand cancer and other diseases at higher resolution level compared to bulk sequencing techniques. In this study, a SC approach was used to analyze intratumoral heterogeneity in four patients with MDS del(5q). Single CD34+CD117+CD45+CD19- bone marrow hematopoietic stem progenitor cells were isolated using the C1 system (Fluidigm) from diagnosis or before receiving any treatment and from available follow-up samples. Selected somatic alterations were further analyzed in SC by high-throughput qPCR (Biomark HD, Fluidigm) using specific TaqMan assays. A median of 175 cells per sample were analyzed. Inferred clonal architectures were relatively simple and either linear or branching. Similar to previous studies based on bulk sequencing to infer clonal architecture, we were able to observe that an ancestral event in one patient can appear as a secondary hit in another one, thus reflecting the high intratumoral heterogeneity in MDS del(5q) and the importance of patient-specific molecular characterization. |
| first_indexed | 2024-03-09T00:48:50Z |
| format | Article |
| id | doaj.art-a5f5d377f8ca4bfba0157dafcaa5e995 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T00:48:50Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a5f5d377f8ca4bfba0157dafcaa5e9952023-12-11T17:22:14ZengMDPI AGCancers2072-66942021-02-0113484110.3390/cancers13040841Analysis of Intratumoral Heterogeneity in Myelodysplastic Syndromes with Isolated del(5q) Using a Single Cell ApproachPamela Acha0Laura Palomo1Francisco Fuster-Tormo2Blanca Xicoy3Mar Mallo4Ana Manzanares5Javier Grau6Silvia Marcé7Isabel Granada8Marta Rodríguez-Luaces9María Diez-Campelo10Lurdes Zamora11Francesc Solé12MDS Group, Institut de Recerca Contra la Leucèmia Josep Carreras, ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, SpainMDS Group, Institut de Recerca Contra la Leucèmia Josep Carreras, ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, SpainMDS Group, Institut de Recerca Contra la Leucèmia Josep Carreras, ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, SpainHematology Service, ICO-Hospital Germans Trias i Pujol, Institut de Recerca Contra la Leucèmia Josep Carreras, Universitat Autònoma de Barcelona, 08916 Badalona, SpainMDS Group, Institut de Recerca Contra la Leucèmia Josep Carreras, ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, SpainMDS Group, Institut de Recerca Contra la Leucèmia Josep Carreras, ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, SpainHematology Service, ICO-Hospital Germans Trias i Pujol, Institut de Recerca Contra la Leucèmia Josep Carreras, Universitat Autònoma de Barcelona, 08916 Badalona, SpainHematology Service, ICO-Hospital Germans Trias i Pujol, Institut de Recerca Contra la Leucèmia Josep Carreras, Universitat Autònoma de Barcelona, 08916 Badalona, SpainHematology Service, ICO-Hospital Germans Trias i Pujol, Institut de Recerca Contra la Leucèmia Josep Carreras, Universitat Autònoma de Barcelona, 08916 Badalona, SpainHematology Service, ICO-Hospital Verge de la Cinta de Tortosa, 43500 Tarragona, SpainHematology Service, Hospital Universitario de Salamanca, 37007 Salamanca, SpainHematology Service, ICO-Hospital Germans Trias i Pujol, Institut de Recerca Contra la Leucèmia Josep Carreras, Universitat Autònoma de Barcelona, 08916 Badalona, SpainMDS Group, Institut de Recerca Contra la Leucèmia Josep Carreras, ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, SpainMyelodysplastic syndromes (MDS) are a heterogeneous group of hematological diseases. Among them, the most well characterized subtype is MDS with isolated chromosome 5q deletion (MDS del(5q)), which is the only one defined by a cytogenetic abnormality that makes these patients candidates to be treated with lenalidomide. During the last decade, single cell (SC) analysis has emerged as a powerful tool to decipher clonal architecture and to further understand cancer and other diseases at higher resolution level compared to bulk sequencing techniques. In this study, a SC approach was used to analyze intratumoral heterogeneity in four patients with MDS del(5q). Single CD34+CD117+CD45+CD19- bone marrow hematopoietic stem progenitor cells were isolated using the C1 system (Fluidigm) from diagnosis or before receiving any treatment and from available follow-up samples. Selected somatic alterations were further analyzed in SC by high-throughput qPCR (Biomark HD, Fluidigm) using specific TaqMan assays. A median of 175 cells per sample were analyzed. Inferred clonal architectures were relatively simple and either linear or branching. Similar to previous studies based on bulk sequencing to infer clonal architecture, we were able to observe that an ancestral event in one patient can appear as a secondary hit in another one, thus reflecting the high intratumoral heterogeneity in MDS del(5q) and the importance of patient-specific molecular characterization.https://www.mdpi.com/2072-6694/13/4/841myelodysplastic syndromessingle cellintratumoral heterogeneity |
| spellingShingle | Pamela Acha Laura Palomo Francisco Fuster-Tormo Blanca Xicoy Mar Mallo Ana Manzanares Javier Grau Silvia Marcé Isabel Granada Marta Rodríguez-Luaces María Diez-Campelo Lurdes Zamora Francesc Solé Analysis of Intratumoral Heterogeneity in Myelodysplastic Syndromes with Isolated del(5q) Using a Single Cell Approach Cancers myelodysplastic syndromes single cell intratumoral heterogeneity |
| title | Analysis of Intratumoral Heterogeneity in Myelodysplastic Syndromes with Isolated del(5q) Using a Single Cell Approach |
| title_full | Analysis of Intratumoral Heterogeneity in Myelodysplastic Syndromes with Isolated del(5q) Using a Single Cell Approach |
| title_fullStr | Analysis of Intratumoral Heterogeneity in Myelodysplastic Syndromes with Isolated del(5q) Using a Single Cell Approach |
| title_full_unstemmed | Analysis of Intratumoral Heterogeneity in Myelodysplastic Syndromes with Isolated del(5q) Using a Single Cell Approach |
| title_short | Analysis of Intratumoral Heterogeneity in Myelodysplastic Syndromes with Isolated del(5q) Using a Single Cell Approach |
| title_sort | analysis of intratumoral heterogeneity in myelodysplastic syndromes with isolated del 5q using a single cell approach |
| topic | myelodysplastic syndromes single cell intratumoral heterogeneity |
| url | https://www.mdpi.com/2072-6694/13/4/841 |
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