Single-Cell DNA Sequencing Reveals an Evolutionary Pattern of CHIP in Transplant Eligible Multiple Myeloma Patients.

Autor:	Borsi E; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', 40138 Bologna, Italy., Vigliotta I; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', 40138 Bologna, Italy., Poletti A; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy., Mazzocchetti G; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy., Solli V; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy., Zazzeroni L; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy., Martello M; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy., Armuzzi S; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy., Taurisano B; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy., Kanapari A; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy., Pistis I; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', 40138 Bologna, Italy., Zamagni E; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', 40138 Bologna, Italy.; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy., Pantani L; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', 40138 Bologna, Italy.; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy., Rocchi S; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', 40138 Bologna, Italy.; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy., Mancuso K; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', 40138 Bologna, Italy.; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy., Tacchetti P; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', 40138 Bologna, Italy.; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy., Rizzello I; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', 40138 Bologna, Italy.; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy., Rizzi S; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', 40138 Bologna, Italy., Dan E; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', 40138 Bologna, Italy., Sinigaglia B; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', 40138 Bologna, Italy., Cavo M; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', 40138 Bologna, Italy.; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy., Terragna C; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', 40138 Bologna, Italy.
Jazyk:	angličtina
Zdroj:	Cells [Cells] 2024 Apr 09; Vol. 13 (8). Date of Electronic Publication: 2024 Apr 09.
DOI:	10.3390/cells13080657
Abstrakt:	Clonal hematopoiesis of indeterminate potential (CHIP) refers to the phenomenon where a hematopoietic stem cell acquires fitness-increasing mutation(s), resulting in its clonal expansion. CHIP is frequently observed in multiple myeloma (MM) patients, and it is associated with a worse outcome. High-throughput amplicon-based single-cell DNA sequencing was performed on circulating CD34+ cells collected from twelve MM patients before autologous stem cell transplantation (ASCT). Moreover, in four MM patients, longitudinal samples either before or post-ASCT were collected. Single-cell sequencing and data analysis were assessed using the MissionBio Tapestri ® platform, with a targeted panel of 20 leukemia-associated genes. We detected CHIP pathogenic mutations in 6/12 patients (50%) at the time of transplant. The most frequently mutated genes were TET2 , EZH2 , KIT , DNMT3A , and ASXL1 . In two patients, we observed co-occurring mutations involving an epigenetic modifier (i.e., DNMT3A) and/or a gene involved in splicing machinery (i.e., SF3B1) and/or a tyrosine kinase receptor (i.e., KIT) in the same clone. Longitudinal analysis of paired samples revealed a positive selection of mutant high-fitness clones over time, regardless of their affinity with a major or minor sub-clone. Copy number analysis of the panel of all genes did not show any numerical alterations present in stem cell compartment. Moreover, we observed a tendency of CHIP-positive patients to achieve a suboptimal response to therapy compared to those without. A sub-clone dynamic of high-fitness mutations over time was confirmed.
Databáze:	MEDLINE
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