Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.
Announcing the new Tapestri scMRD Assay for AML. Learn More

Personalized single-cell proteogenomics to distinguish acute myeloid leukemia from nonmalignant clonal hematopoiesis

Dillon, L.W. et al.
Blood Cancer Discovery (2021)

Genetic mutations associated with acute myeloid leukemia (AML) also occur in agerelated clonal hematopoiesis, often in the same individual. This makes confident assignment of detected variants to malignancy challenging. The issue is particularly crucial for AML posttreatment measurable residual disease monitoring, where results can be discordant between genetic sequencing and flow cytometry. We show here that it is possible to distinguish AML from clonal hematopoiesis and to resolve the immunophenotypic identity of clonal architecture. To achieve this, we first design patient-specific DNA probes based on patient’s whole-genome sequencing and then use them for patient-personalized single-cell DNA sequencing with simultaneous single-cell antibody–oligonucleotide sequencing. Examples illustrate AML arising from DNMT3A- and TET2-mutated clones as well as independently. The ability to personalize single-cell proteogenomic assessment for individual patients based on leukemia-specific genomic features has implications for ongoing AML precision medicine efforts.


Dillon, L.W., Ghannam, J., Nosiri, C., Gui, G., Goswami, M., Calvo, K.R., Lindblad, K.E., Oetjen, K.A., Wilkerson, M., Soltis, A.R., Sukumar, G., Dalgard, C.L., Thompson, J., Valdez, J., DeStefano, C.B., Lai1, C., Sciambi, A., Durruthy-Durruthy, R., Llanso, A, Gulati, S, Wang, S., Ooi, A., Dagur, P.K., McCoy, J.P., Burr, P., Li, Y., Hourigan, C.S.


scTAM-seq enables targeted high-confidence analysis of DNA methylation in single cells
Bianchi A
Genome Biology (2022)
Single cell genotypic and phenotypic analysis of measurable residual disease in acute myeloid leukemia
Troy T. Robinson
BioRxiv (2022)
The genomic landscape of pediatric acute lymphoblastic leukemia
Samuel W. Brady
Nature Genetics
Single‑cell DNA sequencing reveals order of mutational acquisition in TRAF7/AKT1 and TRAF7/KLF4 mutant meningiomas
Helin Dogan
Acta Neuropathologica