DNA methylation dynamic of bone marrow hematopoietic stem cells after allogeneic transplantation
Abstract Background Allogeneic hematopoietic stem cell transplantation (AHSCT) is a curative therapeutic approach for different hematological malignancies (HMs), and epigenetic modifications, including DNA methylation, play a role in the reconstitution of the hematopoietic system after AHSCT. This s...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-05-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-019-1245-6 |
| _version_ | 1828910218917969920 |
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| author | Stefania Trino Pietro Zoppoli Angelo Michele Carella Ilaria Laurenzana Alessandro Weisz Domenico Memoli Giovanni Calice Francesco La Rocca Vittorio Simeon Lucia Savino Luigi Del Vecchio Pellegrino Musto Antonella Caivano Luciana De Luca |
| author_facet | Stefania Trino Pietro Zoppoli Angelo Michele Carella Ilaria Laurenzana Alessandro Weisz Domenico Memoli Giovanni Calice Francesco La Rocca Vittorio Simeon Lucia Savino Luigi Del Vecchio Pellegrino Musto Antonella Caivano Luciana De Luca |
| author_sort | Stefania Trino |
| collection | DOAJ |
| description | Abstract Background Allogeneic hematopoietic stem cell transplantation (AHSCT) is a curative therapeutic approach for different hematological malignancies (HMs), and epigenetic modifications, including DNA methylation, play a role in the reconstitution of the hematopoietic system after AHSCT. This study aimed to explore global DNA methylation dynamic of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) from donors and their respective recipients affected by acute myeloid leukemia (AML), acute lymphoid leukemia (ALL) and Hodgkin lymphoma (HL) during the first year after transplant. Methods We measured DNA methylation profile by Illumina HumanMethylationEPIC in BM HSPC of 10 donors (t0) and their matched recipients at different time points after AHSCT, at day + 30 (t1), + 60 (t2), + 120 (t3), + 180 (t4), and + 365 (t5). Differential methylation analysis was performed by using R software and CRAN/Bioconductor packages. Gene set enrichment analysis was carried out on promoter area of significantly differentially methylated genes by clusterProfiler package and the mSigDB genes sets. Results Results show significant differences in the global methylation profile between HL and acute leukemias, and between patients with mixed and complete chimerism, with a strong methylation change, with prevailing hyper-methylation, occurring 30 days after AHSCT. Functional analysis of promoter methylation changes identified genes involved in hematopoietic cell activation, differentiation, shaping, and movement. This could be a consequence of donor cell “adaptation” in recipient BM niche. Interestingly, this epigenetic remodeling was reversible, since methylation returns similar to that of donor HSPCs after 1 year. Only for a pool of genes, mainly involved in dynamic shaping and trafficking, the DNA methylation changes acquired after 30 days were maintained for up to 1 year post-transplant. Finally, preliminary data suggest that the methylation profile could be used as predictor of relapse in ALL. Conclusions Overall, these data provide insights into the DNA methylation changes of HSPCs after transplantation and a new framework to investigate epigenetics of AHSCT and its outcomes. |
| first_indexed | 2024-12-13T18:40:08Z |
| format | Article |
| id | doaj.art-e0ec02ce47b3405ea8a4e1db069d740f |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-13T18:40:08Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-e0ec02ce47b3405ea8a4e1db069d740f2022-12-21T23:35:15ZengBMCStem Cell Research & Therapy1757-65122019-05-0110111310.1186/s13287-019-1245-6DNA methylation dynamic of bone marrow hematopoietic stem cells after allogeneic transplantationStefania Trino0Pietro Zoppoli1Angelo Michele Carella2Ilaria Laurenzana3Alessandro Weisz4Domenico Memoli5Giovanni Calice6Francesco La Rocca7Vittorio Simeon8Lucia Savino9Luigi Del Vecchio10Pellegrino Musto11Antonella Caivano12Luciana De Luca13Laboratory of Preclinical and Translational Research, IRCCS - Referral Cancer Center of Basilicata (CROB)Laboratory of Preclinical and Translational Research, IRCCS - Referral Cancer Center of Basilicata (CROB)SSD Unità di terapia intensiva ematologica e terapie cellulari, Fondazione IRCCS-Casa Sollievo della SofferenzaLaboratory of Preclinical and Translational Research, IRCCS - Referral Cancer Center of Basilicata (CROB)Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry Scuola Medica Salernitana, University of SalernoLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry Scuola Medica Salernitana, University of SalernoLaboratory of Preclinical and Translational Research, IRCCS - Referral Cancer Center of Basilicata (CROB)Laboratory of Clinical Research and Advanced Diagnostics, IRCCS - Referral Cancer Center of Basilicata (CROB)Medical Statistics Unit, University of Campania “Luigi Vanvitelli”SSD Unità di terapia intensiva ematologica e terapie cellulari, Fondazione IRCCS-Casa Sollievo della SofferenzaDepartment of Molecular Medicine and Medical Biotechnologies, University of Naples Federico IIUnit of Hematology and Stem Cell Transplantation, IRCCS - Referral Cancer Center of Basilicata (CROB)Laboratory of Preclinical and Translational Research, IRCCS - Referral Cancer Center of Basilicata (CROB)Laboratory of Preclinical and Translational Research, IRCCS - Referral Cancer Center of Basilicata (CROB)Abstract Background Allogeneic hematopoietic stem cell transplantation (AHSCT) is a curative therapeutic approach for different hematological malignancies (HMs), and epigenetic modifications, including DNA methylation, play a role in the reconstitution of the hematopoietic system after AHSCT. This study aimed to explore global DNA methylation dynamic of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) from donors and their respective recipients affected by acute myeloid leukemia (AML), acute lymphoid leukemia (ALL) and Hodgkin lymphoma (HL) during the first year after transplant. Methods We measured DNA methylation profile by Illumina HumanMethylationEPIC in BM HSPC of 10 donors (t0) and their matched recipients at different time points after AHSCT, at day + 30 (t1), + 60 (t2), + 120 (t3), + 180 (t4), and + 365 (t5). Differential methylation analysis was performed by using R software and CRAN/Bioconductor packages. Gene set enrichment analysis was carried out on promoter area of significantly differentially methylated genes by clusterProfiler package and the mSigDB genes sets. Results Results show significant differences in the global methylation profile between HL and acute leukemias, and between patients with mixed and complete chimerism, with a strong methylation change, with prevailing hyper-methylation, occurring 30 days after AHSCT. Functional analysis of promoter methylation changes identified genes involved in hematopoietic cell activation, differentiation, shaping, and movement. This could be a consequence of donor cell “adaptation” in recipient BM niche. Interestingly, this epigenetic remodeling was reversible, since methylation returns similar to that of donor HSPCs after 1 year. Only for a pool of genes, mainly involved in dynamic shaping and trafficking, the DNA methylation changes acquired after 30 days were maintained for up to 1 year post-transplant. Finally, preliminary data suggest that the methylation profile could be used as predictor of relapse in ALL. Conclusions Overall, these data provide insights into the DNA methylation changes of HSPCs after transplantation and a new framework to investigate epigenetics of AHSCT and its outcomes.http://link.springer.com/article/10.1186/s13287-019-1245-6Allogeneic hematopoietic bone marrow stem cell transplantationHematopoietic stem and progenitor cellsDNA methylationCpG sitesHematological malignanciesPromoter methylation region |
| spellingShingle | Stefania Trino Pietro Zoppoli Angelo Michele Carella Ilaria Laurenzana Alessandro Weisz Domenico Memoli Giovanni Calice Francesco La Rocca Vittorio Simeon Lucia Savino Luigi Del Vecchio Pellegrino Musto Antonella Caivano Luciana De Luca DNA methylation dynamic of bone marrow hematopoietic stem cells after allogeneic transplantation Stem Cell Research & Therapy Allogeneic hematopoietic bone marrow stem cell transplantation Hematopoietic stem and progenitor cells DNA methylation CpG sites Hematological malignancies Promoter methylation region |
| title | DNA methylation dynamic of bone marrow hematopoietic stem cells after allogeneic transplantation |
| title_full | DNA methylation dynamic of bone marrow hematopoietic stem cells after allogeneic transplantation |
| title_fullStr | DNA methylation dynamic of bone marrow hematopoietic stem cells after allogeneic transplantation |
| title_full_unstemmed | DNA methylation dynamic of bone marrow hematopoietic stem cells after allogeneic transplantation |
| title_short | DNA methylation dynamic of bone marrow hematopoietic stem cells after allogeneic transplantation |
| title_sort | dna methylation dynamic of bone marrow hematopoietic stem cells after allogeneic transplantation |
| topic | Allogeneic hematopoietic bone marrow stem cell transplantation Hematopoietic stem and progenitor cells DNA methylation CpG sites Hematological malignancies Promoter methylation region |
| url | http://link.springer.com/article/10.1186/s13287-019-1245-6 |
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