{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T01:50:16Z","timestamp":1789696216390,"version":"4.0.1"},"reference-count":40,"publisher":"American Society of Hematology","issue":"14","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,28]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Myeloproliferative neoplasms (MPNs) are caused by acquired mutations in hematopoietic stem and progenitor cells (HSPCs). The acquisition of additional mutations, such as TP53, and the overall mutational burden influence a patient\u2019s risk of disease progression to lethal post-MPN acute myeloid leukemias (AML). Recent technological advancements in linking single-cell gene expression with genotype have improved our understanding of tumor heterogeneity. However, current methodologies have limitations in simultaneously genotyping low-expression genes (such as JAK2) alongside other pathogenic loci. To address this, we developed a novel long-read genotyping pipeline of complementary DNA transcripts (long-read genotyping of transcripts [LOTR]-Seq), which can genotype the full length of expressed transcripts from 30 genes at once. Using LOTR-Seq, we genotyped HSPCs at the JAK2V617 locus in 9075 single cells from 8 patients with chronic-phase MPN (CP-MPN) and in 5016 cells from 4 patients with post-MPN AML. We then linked the mutations to the single-cell transcriptomes of 29\u2009712 JAK2V617F-driven CP-MPN cells and 16\u2009895 post-MPN AML cells. In our analysis of post-MPN AML, we identified 9 mutated loci across 6 genes (JAK2, IDH1\/2, TP53, SRSF2, and U2AF1) and linked these mutations to specific transcriptional phenotypes. Overall, LOTR-Seq provides novel insights into the evolution of post-MPN AML.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/bloodadvances.2025018902","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T14:15:02Z","timestamp":1778249702000},"page":"5016-5030","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":3,"title":["Single-cell long-read genotyping of transcripts reveals discrete mechanisms of clonal evolution in post-MPN AML"],"prefix":"10.1182","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5168-050X","authenticated-orcid":false,"given":"Julian","family":"Grabek","sequence":"first","affiliation":[{"name":"1Cancer Research Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia"},{"name":"2Faculty of Medicine, The University of Queensland, St Lucia, Brisbane, QLD, 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