journal contribution
posted on 2023-07-05, 08:42 authored by Andriana G. Kotini, Saul Carcamo, Nataly Cruz-Rodriguez, Malgorzata Olszewska, Tiansu Wang, Deniz Demircioglu, Chan-Jung Chang, Elsa Bernard, Mark P. Chao, Ravindra Majeti, Hanzhi Luo, Michael G. Kharas, Dan Hasson, Eirini P. Papapetrou Table S1. Patient characteristics. AML: acute myeloid leukemia; MDS: myelodysplastic syndrome; MPN: myeloproliferative neoplasm; ET: essential thrombocythemia; PBMCs: peripheral blood mononuclear cells; BMMCs: bone marrow mononuclear cells; PDX: patient-derived xenografts
Table S2. All patient samples used in this study with genetic characterization and reprogramming outcomes. Blue font denotes partially reprogrammed (as opposed to bona fide iPSC) colonies and clones.
Table S3. All AML-iPSC lines phenotypically characterized.
Table S4. Top 50 upregulated genes (highest log2 fold change) in each cluster.
Table S5. Primers used for genotyping.
Table S6. Primers used for qRT-PCR analyses.
Funding
National Institutes of Health (NIH)
Leukemia and Lymphoma Society (LLS)
American Association for Cancer Research (AACR)
Edward P. Evans Foundation
New York State Stem Cell Science (NYSTEM)
History
ARTICLE ABSTRACT
The reprogramming of human acute myeloid leukemia (AML) cells into induced pluripotent stem cell (iPSC) lines could provide new faithful genetic models of AML, but is currently hindered by low success rates and uncertainty about whether iPSC-derived cells resemble their primary counterparts. Here we developed a reprogramming method tailored to cancer cells, with which we generated iPSCs from 15 patients representing all major genetic groups of AML. These AML-iPSCs retain genetic fidelity and produce transplantable hematopoietic cells with hallmark phenotypic leukemic features. Critically, single-cell transcriptomics reveal that, upon xenotransplantation, iPSC-derived leukemias faithfully mimic the primary patient-matched xenografts. Transplantation of iPSC-derived leukemias capturing a clone and subclone from the same patient allowed us to isolate the contribution of a FLT3-ITD mutation to the AML phenotype. The results and resources reported here can transform basic and preclinical cancer research of AML and other human cancers.
We report the generation of patient-derived iPSC models of all major genetic groups of human AML. These exhibit phenotypic hallmarks of AML in vitro and in vivo, inform the clonal hierarchy and clonal dynamics of human AML, and exhibit striking similarity to patient-matched primary leukemias upon xenotransplantation.See related commentary by Doulatov, p. 252.This article is highlighted in the In This Issue feature, p. 247
