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. 2022 Aug 3;13:4517. doi: 10.1038/s41467-022-32145-y

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 7 — At baseline, patient #12 presented with a t(4;14) and the same clonal composition was seen at the left and right iliac crest. The first follow-up (FU) sample was collected from a sacrum lesion after the sixth treatment line. The dominant subclone (blue branch) was positive for the SBS-MM1 signature, indicating a single-cell expansion. The precursor (gray) of this subclone was already detectable at baseline. Two months later, a sample was collected from the right iliac crest. While the focal lesion subclone was detectable at the minor level, another SBS-MM1-positive subclone with an MYC translocation (green branch) dominated at this location, suggesting clonal co-existence or competition. Despite extensive treatment, a very similar clonal composition was seen in two focal lesions and six iliac crest samples. However, after another autologous stem cell transplantation (sixth FU), the patient achieved a complete remission (CR) and a subclone emerged, which was not seen in prior samples (red branch). This del(17p) and signature SBS-MM1 positive subclone, which dominated at the iliac crest at the last available time point, shared the preexisting precursor with the other two relapse subclones but represented another branch. Single-cell expansions were predicted based on the presence of the SBS-MM1 melphalan signature. The boxes show the proportion of detected subclones, with each subclone having a distinct color. Dashed lines illustrate the origin/relationship of subclones/branches. For instance, all subclones of the “blue branch” are interconnected by a blue dashed line. The length of branches of the phylogenetic tree corresponds to the time point of the first appearance of respective clones. For convenience, only known myeloma drivers and mutations affecting two members of the KDM/KMT gene family are shown in the mock phylogenetic tree. A more detailed description is shown in Suppl. Fig. 14. Please note that due to limited space, data for a sample after the 11th treatment line is only presented in the Suppl. Fig. 14. SD stable disease, PD progressive disease, VGPR very good partial remission. Source data are provided as a Source Data file.