---
title: "CLEC12A/CD84 dual targeting maps antigen landscape in paediatric AML LSCs"
id: "biorxiv-15-recurrent-leukaemia-stem-cell-states-define-the-antigenic-landscape-of"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-15-recurrent-leukaemia-stem-cell-states-define-the-antigenic-landscape-of"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.19.760044v1?rss=1"
published_at: "2026-10-23T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# CLEC12A/CD84 dual targeting maps antigen landscape in paediatric AML LSCs
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-15-recurrent-leukaemia-stem-cell-states-define-the-antigenic-landscape-of
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.19.760044v1?rss=1)
- **Published At:** 2026-10-23T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Investigators used single-cell transcriptomics combined with surface proteomics (CITE-seq) to map malignant cells in paediatric acute myeloid leukaemia. - The study team applied an integrated framework for malignant cell identification and unbiased gene-program discovery. - Data indicated three conserved **leukaemia stem cell (LSC)** states across patients: primitive (P-LSC), monocytic (M-LSC), and erythroid-like (E-LSC). - These three LSC states often coexist within individual patients and display distinct transcriptional programmes and immunophenotypes. - Quantitative surface antigen profiling showed no single antigen provided full LSC coverage across all states. - Authors reported **CLEC12A** expression across P-LSC and M-LSC but noted it was largely absent from E-LSC. - The cohort showed **CD84** provided complementary coverage, including serving as the dominant antigen in the E-LSC population. - Combining **CLEC12A** and **CD84** yielded broad coverage across all three LSC subtypes while sparing healthy haematopoietic stem cells, according to the reported profiling. - Validation analyses across independent single-cell and bulk cohorts confirmed robustness of the CLEC12A/CD84 combination, the authors noted. - The report did not include clinical trial efficacy data or in vivo CAR T–cell testing details; the source framed findings as a paediatric-specific framework for antigen prioritisation and a blueprint for rational CAR T-cell combination design.
## Clinical Analysis & Structured Key Points
Recurrent leukaemia stem cell states define the antigenic landscape of paediatric Acute Myeloid Leukaemia | bioRxiv Skip to main content New Results Recurrent leukaemia stem cell states define the antigenic landscape of paediatric Acute Myeloid Leukaemia Sina Kanannejad , Macarena Oporto Espuelas , Claudia D'Oria , Filippo Martignano , Ilaria Marina Michelozzi , Soumick Chatterjee , Edoardo Giacopuzzi , Eduardo Gomez Castaneda , Aurora Casiraghi , Theodoros Xenakis , George T. Hall , Efstratios Kirtsios , Cecilia Reyneri , Hannah Macpherson , Jack Bartram , Rebecca Thomas , Sergi Castellano , Persis J. Amrolia , View ORCID Profile Alice Giustacchini doi: https://doi.org/10.64898/2026.10.19.760044 Sina Kanannejad 1 Genomics Research Centre, Human Technopole, Milan, Italy; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Macarena Oporto Espuelas 2 Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Claudia D'Oria 1 Genomics Research Centre, Human Technopole, Milan, Italy; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Filippo Martignano 1 Genomics Research Centre, Human Technopole, Milan, Italy; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ilaria Marina Michelozzi 2 Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Soumick Chatterjee 3 Genomics Research Centre, Human Technopole, Milan, Italy; Faculty of Computer Science, Otto von Guericke University Magdeburg, Magdeburg, Germany; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Edoardo Giacopuzzi 1 Genomics Research Centre, Human Technopole, Milan, Italy; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Eduardo Gomez Castaneda 2 Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Aurora Casiraghi 1 Genomics Research Centre, Human Technopole, Milan, Italy; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Theodoros Xenakis 4 Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; Find this author on Google Scholar Find this author on PubMed Search for this author on this site George T. Hall 4 Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Efstratios Kirtsios 2 Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Cecilia Reyneri 1 Genomics Research Centre, Human Technopole, Milan, Italy; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Hannah Macpherson 4 Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jack Bartram 5 Great Ormond Street Hospital for Children, London, United Kingdom; North Thames Genomic Laboratory Hub, London, United Kingdom; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Rebecca Thomas 6 Department of Haematology, Great Ormond Street Hospital, London, United Kingdom; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Sergi Castellano 4 Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Persis J. Amrolia 7 Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; Bone Marrow Transplant Department, Great Ormond Street Hospital, London, United Kingdom; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Alice Giustacchini 8 Genomics Research Centre, Human Technopole, Milan, Italy; Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, United Kingdom Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Alice Giustacchini For correspondence: a.giustacchini{at}ucl.ac.uk Abstract Info/History Metrics Supplementary material Preview PDF Abstract Paediatric acute myeloid leukaemia (pAML) remains a leading cause of childhood cancer mortality, with disease heterogeneity representing a major obstacle to effective immunotherapy. To enable rational immunotherapy design accounting for such heterogeneity, we combined single-cell transcriptomics and surface proteomics (CITE-seq). Using an integrated framework for malignant cell identification and unbiased gene program identification, we resolved three conserved leukaemia stem cell (LSC) subtypes, primitive (P-LSC), monocytic (M-LSC), and erythroid-like (E-LSC), that frequently coexist within individual patients in varying proportions and represent distinct stem-cell states with characteristic immunophenotypes and transcriptional programmes. Quantitative surface antigen profiling revealed that no single target achieved full LSC coverage. CLEC12A, an antigen currently being evaluated clinically, was expressed across P-LSC and M-LSC but was largely absent from E-LSC. In contrast, CD84 provided complementary coverage in the P and M groups and served as the primary target in the E-LSC population. The combination of CLEC12A and CD84 provided broad coverage across all three LSC subtypes, while sparing healthy haematopoietic stem cells. Validation across independent single-cell and bulk cohorts confirmed the robustness of this combination. These findings establish a paediatric-specific framework for antigen prioritisation in AML, identify CLEC12A/CD84 as a robust dual-targeting strategy across heterogeneous LSC states, and provide a blueprint for the rational design of next-generation CAR T-cell combinations. Competing Interest Statement The authors have declared no competing interest. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Back to top Previous Next Posted October 23, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Recurrent leukaemia stem cell states define the antigenic landscape of paediatric Acute Myeloid Leukaemia Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Recurrent leukaemia stem cell states define the antigenic landscape of paediatric Acute Myeloid Leukaemia Sina Kanannejad , Macarena Oporto Espuelas , Claudia D'Oria , Filippo Martignano , Ilaria Marina Michelozzi , Soumick Chatterjee , Edoardo Giacopuzzi , Eduardo Gomez Castaneda , Aurora Casiraghi , Theodoros Xenakis , George T. Hall , Efstratios Kirtsios , Cecilia Reyneri , Hannah Macpherson , Jack Bartram , Rebecca Thomas , Sergi Castellano , Persis J. Amrolia , Alice Giustacchini bioRxiv 2026.10.19.760044; doi: https://doi.org/10.64898/2026.10.19.760044 Share This Article: Copy Citation Tools Recurrent leukaemia stem cell states define the antigenic landscape of paediatric Acute Myeloid Leukaemia Sina Kanannejad , Macarena Oporto Espuelas , Claudia D'Oria , Filippo Martignano , Ilaria Marina Michelozzi , Soumick Chatterjee , Edoardo Giacopuzzi , Eduardo Gomez Castaneda , Aurora Casiraghi , Theodoros Xenakis , George T. Hall , Efstratios Kirtsios , Cecilia Reyneri , Hannah Macpherson , Jack Bartram , Rebecca Thomas , Sergi Castellano , Persis J. 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