Studying Clonal Evolution of Myeloid Malignancies Using Induced Pluripotent Stem Cells

Overview

Journal Curr Opin Hematol

Specialty Hematology

Date 2020 Dec 2

PMID 33264225

Citations 5

Authors

Sergei Doulatov

Eirini P Papapetrou

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: Myeloid malignancies comprise a spectrum of genetically heterogeneous disorders marked by the stepwise acquisition of somatic mutations and clonal evolution. The blood and bone marrow of patients typically consists of a mix of different clones and subclones along the path of clonal evolution that cannot be deconvoluted with most current approaches. Here, we review the application of induced pluripotent stem cell (iPSC) technology to the study of the clonal architecture and clonal evolution of these diseases, focusing on myelodysplastic syndromes and acute myeloid leukemia.

Recent Findings: Reprogramming to pluripotency allows capture of the genomes of single somatic cells into stable iPSC lines. In addition, precise genome editing can introduce specific driver mutations, isolated, and in combinations, into normal iPSCs. Studies utilizing these approaches have elucidated the clonal composition and mutational order in patients with myeloid neoplasms. Importantly, they have also enabled functional interrogation of the cellular and molecular consequences of individual mutations and their combinations and allowed testing of the effects of drugs on distinct disease clones.

Summary: Human iPSCs are important tools to elucidate the mechanisms of progression from normal to malignant haematopoiesis and empower drug testing and drug discovery.

Citing Articles

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Monoallelic KRAS (G13C) mutation triggers dysregulated expansion in induced pluripotent stem cell-derived hematopoietic progenitor cells.

Lin H, Takagi M, Kubara K, Yamazaki K, Michikawa F, Okumura T Stem Cell Res Ther. 2024; 15(1):106.

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Reprogramming of Acute Myeloid Leukemia Patients Cells: Harboring Cancer Mutations Requires Targeting of AML Hierarchy.

Golubeva D, Porras D, Doyle M, Reid J, Tanasijevic B, Boyd A Stem Cells Transl Med. 2023; 12(6):334-354.

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Sandmann S, Behrens Y, Davenport C, Thol F, Heuser M, Dorfel D Front Oncol. 2022; 12:888114.

PMID: 35875134 PMC: 9305660. DOI: 10.3389/fonc.2022.888114.

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