ArticleCell stem cell2017
Stage-Specific Human Induced Pluripotent Stem Cells Map the Progression of Myeloid Transformation to Transplantable Leukemia.
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Article in Cell stem cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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89citing papers in PubMed
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Who cites it
89 citing papers in PubMed.
- Pan-cancer analysis of single-cell profiles with polygenic signals reveals genetic influences on tumor immunity across cancers.Communications biology · 2026Article
- Sustained MYC overexpression drives myeloid differentiation block and acquisition of leukemic phenotypes.Experimental hematology · 2026Article
- Ontogeny Dictates Oncogenic Potential, Lineage Hierarchy, and Therapy Response in Pediatric Leukemia.Cancer discovery · 2026Article
- Targeting dysregulated epigenetic and transcription factor networks inBlood neoplasia · 2026Article
- Optical genome mapping as a high-resolution tool for uncovering cytogenetic complex and cryptic alterations in a cohort of patients with MDS and AML.NPJ precision oncology · 2026Article
- Modeling myeloid cell development in health and disease using induced pluripotent stem cells.Frontiers in immunology · 2026Review
- Human iPSCs-based modeling unveils SETBP1 as a driver of chromatin rewiring in GATA2 deficiency.Nature communications · 2025Article
- SF3B1-mutant models of RNA mis-splicing uncover UBA1 as a therapeutic target in myelodysplastic neoplasms.Leukemia · 2025Article
- Long-term engrafting multilineage hematopoietic cells differentiated from human induced pluripotent stem cells.Nature biotechnology · 2025Article
- Human iPSC-based breast cancer model identifies S100P-dependent cancer stemness induced byScience advances · 2025Article
- Article
- A heterozygous CEBPA mutation disrupting the bZIP domain in a RUNX1 and SRSF2 mutational background causes MDS disease progression.Nature communications · 2025Article
- Protocol for the generation of HLF+ HOXA+ human hematopoietic progenitor cells from pluripotent stem cells.STAR protocols · 2025Article
- The Crossroads of Clonal Evolution, Differentiation Hierarchy, and Ontogeny in Leukemia Development.Blood cancer discovery · 2025Review
- Understanding Human Oncogene Function and Cooperativity in Myeloid Malignancy Using iPSCs.Experimental hematology · 2025Review
- Examining patient-specific responses to PARP inhibitors in a novel, human induced pluripotent stem cell-based model of breast cancer.NPJ precision oncology · 2025Article
- Metabolic adaptations to acute glucose uptake inhibition converge upon mitochondrial respiration for leukemia cell survival.Cell communication and signaling : CCS · 2025Article
- Article
- CRISPR Dependency Screens in Primary Hematopoietic Stem Cells Identify KDM3B as a Genotype-specific Vulnerability in IDH2- and TET2-mutant Cells.Cancer discovery · 2024Article
- Lineage-tracing hematopoietic stem cell origins in vivo to efficiently make human HLF+ HOXA+ hematopoietic progenitors from pluripotent stem cells.Developmental cell · 2024Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors.
Andriana G KotiniDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Chan-Jung ChangDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Arthur ChowMolecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Han YuanComputational Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Tzu-Chieh HoMolecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Tiansu WangDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Shailee VoraDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Alexander SolovyovDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Chrystel HusserDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Malgorzata OlszewskaDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Julie Teruya-FeldsteinDepartment of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Deepak PerumalDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Virginia M KlimekDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Alexandros SpyridonidisSchool of Medicine, University of Patras, Patras 26504, Greece.
Raajit K RampalDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Lewis SilvermanTisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
E Premkumar ReddyTisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Elli PapaemmanuilDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Samir ParekhDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Benjamin D GreenbaumDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Christina S LeslieComputational Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Michael G KharasMolecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: kharasm@mskcc.org.
Eirini P PapapetrouDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: eirini.papapetrou@mssm.edu.
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MTHE TISCH CANCER INSTITUTE - CANCER CENTER SUPPORT GRANTP30CA196521 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Deanna L Benson · 2015 to 2026
$35.4MTRAINING PROGRAM IN CANCER THERAPYT32CA078207 · NCI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI James J Manfredi · 1999 to 2026
$11.6MUncovering the role for MSI2 network in hematopoietic stem cellsR01DK101989 · NIDDK · SLOAN-KETTERING INST CAN RESEARCH · PI Michael Kharas, Vijay Ganesh Sankaran · 2014 to 2026
$6.2MCharacterizing the MSI2 network in leukemiaR01CA193842 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI KHARAS, MICHAEL · 2015 to 2025
$4.1MTri-Institutional Training Program in Computational Biology & MedicineT32GM083937 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHRISTINI, DAVID J. · 2009 to 2018
$3.1MModeling chromosome 7 loss in Myelodysplasia-iPSCsR01HL121570 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI PAPAPETROU, EIRINI · 2014 to 2018
$2.1MGenomic profiling and development of murine models of transformation of MPNsK08CA188529 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI RAMPAL, RAAJIT · 2014 to 2018
$891kGenetic correction of human beta-thalassemic induced pluripotent stem cellsR00DK087923 · NIDDK · UNIVERSITY OF WASHINGTON · PI PAPAPETROU, EIRINI · 2013 to 2015
$760kCancer Research UK 21019NCI NIH HHS K08 CA188529NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA196521NCI NIH HHS R01 CA193842NCI NIH HHS T32 CA078207NHLBI NIH HHS R01 HL121570NIDDK NIH HHS R00 DK087923NIDDK NIH HHS R01 DK101989NIGMS NIH HHS T32 GM083937
Abstract
Myeloid malignancy is increasingly viewed as a disease spectrum, comprising hematopoietic disorders that extend across a phenotypic continuum ranging from clonal hematopoiesis to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In this study, we derived a collection of induced pluripotent stem cell (iPSC) lines capturing a range of disease stages encompassing preleukemia, low-risk MDS, high-risk MDS, and secondary AML. Upon their differentiation, we found hematopoietic phenotypes of graded severity and/or stage specificity that together delineate a phenotypic roadmap of disease progression culminating in serially transplantable leukemia. We also show that disease stage transitions, both reversal and progression, can be modeled in this system using genetic correction or introduction of mutations via CRISPR/Cas9 and that this iPSC-based approach can be used to uncover disease-stage-specific responses to drugs. Our study therefore provides insight into the cellular events demarcating the initiation and progression of myeloid transformation and a new platform for testing genetic and pharmacological interventions.
Indexed as
Disease ProgressionAnimalsAntineoplastic AgentsCell Transformation, NeoplasticCellular ReprogrammingDNA Mutational AnalysisGene Expression Regulation, LeukemicHematopoietic Stem CellsHumansInduced Pluripotent Stem CellsLeukemia, Myeloid, AcuteMiceModels, BiologicalMyelodysplastic SyndromesNeoplasm TransplantationPhenotypeAntineoplastic Agentsacute myeloid leukemiacancer progressionhPSC-derived hematopoiesisinduced pluripotent stem cellsiPSC disease modelingleukemialeukemia progressionmyelodysplastic syndromemyeloid malignancytransplantation
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