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Clonal dynamics of donor-derived myelodysplastic syndrome after unrelated hematopoietic cell transplantation for high-risk pediatric B-lymphoblastic leukemia

Donor-derived hematologic malignancies are rare complications of hematopoietic cell transplantation (HCT). Although these are commonly either a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), in general, they are a heterogeneous group of diseases, and a unified mechanism for their de...

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Autores principales: Schwartz, Jason R., Walsh, Michael P., Ma, Jing, Lamprecht, Tamara, Wang, Shuoguo, Wu, Gang, Raimondi, Susana, Triplett, Brandon M., Klco, Jeffery M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169831/
https://www.ncbi.nlm.nih.gov/pubmed/29891567
http://dx.doi.org/10.1101/mcs.a002980
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author Schwartz, Jason R.
Walsh, Michael P.
Ma, Jing
Lamprecht, Tamara
Wang, Shuoguo
Wu, Gang
Raimondi, Susana
Triplett, Brandon M.
Klco, Jeffery M.
author_facet Schwartz, Jason R.
Walsh, Michael P.
Ma, Jing
Lamprecht, Tamara
Wang, Shuoguo
Wu, Gang
Raimondi, Susana
Triplett, Brandon M.
Klco, Jeffery M.
author_sort Schwartz, Jason R.
collection PubMed
description Donor-derived hematologic malignancies are rare complications of hematopoietic cell transplantation (HCT). Although these are commonly either a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), in general, they are a heterogeneous group of diseases, and a unified mechanism for their development has remained elusive. Here we report next-generation sequencing, including whole-exome sequencing (WES), whole-genome sequencing (WGS), and targeted sequencing, of a case of donor-derived MDS (dMDS) following HCT for high-risk B-lymphoblastic leukemia (B-ALL) in an adolescent. Through interrogation of single-nucleotide polymorphisms (SNPs) in the WGS data, we unequivocally prove that the MDS is donor-derived. Additionally, we sequenced 15 samples from 12 time points, including the initial B-ALL diagnostic sample through several post-HCT remission samples, the dMDS, and representative germline samples from both patient and donor, to show that the MDS-related pathologic mutations, including a canonical ASXL1 (p.Y700*) mutation, were detectable nearly 3 yr prior to the morphological detection of MDS. Furthermore, these MDS mutations were not detectable immediately following, and for >1 yr post-, HCT. These data support the clinical utility of comprehensive sequencing following HCT to detect donor-derived malignancies, while providing insights into the clonal progression of dMDS over a 4-yr period.
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spelling pubmed-61698312018-10-12 Clonal dynamics of donor-derived myelodysplastic syndrome after unrelated hematopoietic cell transplantation for high-risk pediatric B-lymphoblastic leukemia Schwartz, Jason R. Walsh, Michael P. Ma, Jing Lamprecht, Tamara Wang, Shuoguo Wu, Gang Raimondi, Susana Triplett, Brandon M. Klco, Jeffery M. Cold Spring Harb Mol Case Stud Research Report Donor-derived hematologic malignancies are rare complications of hematopoietic cell transplantation (HCT). Although these are commonly either a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), in general, they are a heterogeneous group of diseases, and a unified mechanism for their development has remained elusive. Here we report next-generation sequencing, including whole-exome sequencing (WES), whole-genome sequencing (WGS), and targeted sequencing, of a case of donor-derived MDS (dMDS) following HCT for high-risk B-lymphoblastic leukemia (B-ALL) in an adolescent. Through interrogation of single-nucleotide polymorphisms (SNPs) in the WGS data, we unequivocally prove that the MDS is donor-derived. Additionally, we sequenced 15 samples from 12 time points, including the initial B-ALL diagnostic sample through several post-HCT remission samples, the dMDS, and representative germline samples from both patient and donor, to show that the MDS-related pathologic mutations, including a canonical ASXL1 (p.Y700*) mutation, were detectable nearly 3 yr prior to the morphological detection of MDS. Furthermore, these MDS mutations were not detectable immediately following, and for >1 yr post-, HCT. These data support the clinical utility of comprehensive sequencing following HCT to detect donor-derived malignancies, while providing insights into the clonal progression of dMDS over a 4-yr period. Cold Spring Harbor Laboratory Press 2018-10 /pmc/articles/PMC6169831/ /pubmed/29891567 http://dx.doi.org/10.1101/mcs.a002980 Text en © 2018 Schwartz et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/) , which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited.
spellingShingle Research Report
Schwartz, Jason R.
Walsh, Michael P.
Ma, Jing
Lamprecht, Tamara
Wang, Shuoguo
Wu, Gang
Raimondi, Susana
Triplett, Brandon M.
Klco, Jeffery M.
Clonal dynamics of donor-derived myelodysplastic syndrome after unrelated hematopoietic cell transplantation for high-risk pediatric B-lymphoblastic leukemia
title Clonal dynamics of donor-derived myelodysplastic syndrome after unrelated hematopoietic cell transplantation for high-risk pediatric B-lymphoblastic leukemia
title_full Clonal dynamics of donor-derived myelodysplastic syndrome after unrelated hematopoietic cell transplantation for high-risk pediatric B-lymphoblastic leukemia
title_fullStr Clonal dynamics of donor-derived myelodysplastic syndrome after unrelated hematopoietic cell transplantation for high-risk pediatric B-lymphoblastic leukemia
title_full_unstemmed Clonal dynamics of donor-derived myelodysplastic syndrome after unrelated hematopoietic cell transplantation for high-risk pediatric B-lymphoblastic leukemia
title_short Clonal dynamics of donor-derived myelodysplastic syndrome after unrelated hematopoietic cell transplantation for high-risk pediatric B-lymphoblastic leukemia
title_sort clonal dynamics of donor-derived myelodysplastic syndrome after unrelated hematopoietic cell transplantation for high-risk pediatric b-lymphoblastic leukemia
topic Research Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169831/
https://www.ncbi.nlm.nih.gov/pubmed/29891567
http://dx.doi.org/10.1101/mcs.a002980
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