Lectures and seminars OnkPat Friday Seminar: Single cell epigenomics and developmental plasticity in acute myeloid leukemia: how different paths lead back to square one

Host: Susanne Schlisio, Department of Oncology-Pathology

Biography

Sander Lambo has joined the department of Oncology-Pathology since August 2026 as an assistant professor. His main research focus is to identify the epigenetic mechanisms that occur in pediatric cancers both during the initiation of the tumor and when tumors relapse. During his postdoctoral studies he investigated the transcriptional and epigenetic cellular plasticity observed in pediatric Acute Myeloid Leukemia after exposure to therapy at Canada's Michael Smith Genome Sciences Centre (2020-2023) and co-developed a new methodology for generating scalable single cell methylation sequencing named Droplet-based Restriction Enzyme and Methylation sequencing (DREAM-seq) at the Dana-Farber Cancer Institute (2023-2026).

Abstract

Pediatric acute myeloid leukemia (pAML) is a disease characterized by outgrowth of early progenitors in the hematopoietic system. Tumor relapse has been associated with an outgrowth of primitive cells termed leukemia stem cells (LSCs). LSCs have the capability to repopulate all cellular hierarchies of the tumor after therapy, independently of any newly acquired genetic events. This seminar will focus on the different epigenetic mechanisms that are involved in repressing differentiation to maintain or form LSCs. The first part will focus on chromatin changes observed after treatment of pAML and how this information can be used to identify mechanisms that key modulators use to repress differentiation. The second part will focus on the DNA methylation dynamics of healthy human bone marrow and how these dynamics are altered upon acquisition of TET2 mutations. Together, the epigenetic mechanisms behind tumor initiation and relapse can be utilized for a better detection of LSCs and to devise therapeutic strategies to specifically target LSCs.

Selected publications

A longitudinal single-cell atlas of treatment response in pediatric AML.
Lambo S, Trinh DL, Ries RE, Jin D, Setiadi A, Ng M, Leblanc VG, Loken MR, Brodersen LE, Dai F, Pardo LM, Ma X, Vercauteren SM, Meshinchi S, Marra MA
Cancer Cell 2023 Dec;41(12):2117-2135.e12

CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias.
Fleming TJ, Antoszewski M, Lambo S, Gundry MC, Piussi R, Wahlster L, Shah S, Reed FE, Dong KD, Paulo JA, Gygi SP, Mimoso C, Goldman SR, Adelman K, Perry JA, Pikman Y, Stegmaier K, Barrachina MN, Machlus KR, Hovestadt V, Arruda A, Minden MD, Voit RA, Sankaran VG
Blood 2025 Dec;146(25):3019-3035