{"entity":{"id":"paper-raajit-rampal-nature-2020","kind":"paper","name":"Single-cell mutation analysis of clonal evolution in myeloid malignancies","aka":[],"tldr":"Paper by Raajit K. Rampal indexed on Europe PMC as PubMed record 33116311, in Nature (2020), one of the most cited records naming an author with this name at Memorial Sloan Kettering Cancer Center.","summary":"Myeloid malignancies, including acute myeloid leukaemia (AML), arise from the expansion of haematopoietic stem and progenitor cells that acquire somatic mutations. Bulk molecular profiling has suggested that mutations are acquired in a stepwise fashion: mutant genes with high variant allele frequencies appear early in leukaemogenesis, and mutations with lower variant allele frequencies are thought to be acquired later 1-3. Although bulk sequencing can provide information about leukaemia biology and prognosis, it cannot distinguish which mutations occur in the same clone(s), accurately measure clonal complexity, or definitively elucidate the order of mutations. To delineate the clonal framework of myeloid malignancies, we performed single-cell mutational profiling on 146 samples from 123 patients. Here we show that AML is dominated by a small number of clones, which frequently harbour co-occurring mutations in epigenetic regulators. Conversely, mutations in signalling genes often occur more than once in distinct subclones, consistent with increasing clonal diversity. We mapped clonal trajectories for each sample and uncovered combinations of mutations that synergized to promote clonal expansion and dominance. Finally, we combined protein expression with mutational analysis to map somatic genotype and clonal architecture with immunophenotype. Our findings provide insights into the pathogenesis of myeloid transformation and how clonal complexity evolves with disease progression.\n\nIndexed on Europe PMC as PubMed record 33116311 (DOI 10.1038/s41586-020-2864-x). Its author list gives \"Rampal R\" with the affiliation \"Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USA\", which names Memorial Sloan Kettering Cancer Center; that is how the record was matched to Raajit K. Rampal, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2020","url":"https://doi.org/10.1038/s41586-020-2864-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33116311/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33116311"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["raajit-rampal"],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2020,"doi":"10.1038/s41586-020-2864-x","pmid":"33116311","authors":"Miles LA, Bowman RL, Merlinsky TR, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Raajit K. Rampal at Memorial Sloan Kettering Cancer Center, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},"route":"/key-papers/paper-raajit-rampal-nature-2020/","neighbours":{"person":[{"id":"raajit-rampal","kind":"person","name":"Raajit K. Rampal","route":"/people/raajit-rampal/"}],"journal":[{"id":"nature","kind":"journal","name":"Nature","route":"/journals/nature/"}]}}