Modeling leukemia with pediatric acute leukemia patient-derived iPSCs

Ting Li; Yingwen Zhang; Yang Li; Xiang Wang; Weiqiao Bao; Jun Huang; Yani Ma; Shanshan Li; Siqi wang; Yi Yang; Yanfeng Liu; Yijin Gao; Haizhong Feng; Yanxin Li

Stem Cell Research (Jul 2021)

Modeling leukemia with pediatric acute leukemia patient-derived iPSCs

Ting Li,
Yingwen Zhang,
Yang Li,
Xiang Wang,
Weiqiao Bao,
Jun Huang,
Yani Ma,
Shanshan Li,
Siqi wang,
Yi Yang,
Yanfeng Liu,
Yijin Gao,
Haizhong Feng,
Yanxin Li

Affiliations

Ting Li: Department of Hematology & Oncology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai 200127, China
Yingwen Zhang: Department of Hematology & Oncology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai 200127, China
Yang Li: Department of Hematology & Oncology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai 200127, China
Xiang Wang: Department of Hematology & Oncology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai 200127, China
Weiqiao Bao: Department of Hematology & Oncology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai 200127, China
Jun Huang: Department of Hematology & Oncology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai 200127, China
Yani Ma: Department of Hematology & Oncology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai 200127, China
Shanshan Li: Department of Hematology & Oncology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai 200127, China
Siqi wang: Department of Hematology & Oncology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai 200127, China
Yi Yang: Department of Hematology & Oncology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai 200127, China
Yanfeng Liu: Department of Hematology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China; Corresponding authors.
Yijin Gao: Department of Hematology & Oncology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai 200127, China; Corresponding authors.
Haizhong Feng: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, Shanghai Cancer Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; Corresponding authors.
Yanxin Li: Department of Hematology & Oncology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai 200127, China; Corresponding authors.

Journal volume & issue: Vol. 54
p. 102404

Abstract

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Objective: ediatric acute leukemia (AL) is the most common hematological malignancy in childhood. However, the limitation of clinical specimens hindered the progress of research. Therefore, new research platforms are urgently needed to establish and clarify the pathogenesis of pediatric AL, and it is necessary to try to find novel targeted therapies for the clinical use. Here, the induced pluripotent stem cells (iPSCs) derived from AL provide a reliable model for basic research. Methods: eukemia cells were sorted by flow cytometry and then reprogrammed into iPSCs by Sendai virus. Cell cycle assay was used to analyze cell proliferation. Results: iPS cell lines from T cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML) cells were successfully established. The reprogramming efficiency of AML cells was much higher than that of ALL cells. Disease iPS cells switched off the expression of the disease marker genes at iPS and HPC stage. When different subtypes of AML-iPSCs were differentiated into hematopoietic progenitor cells, iPS derived from acute megakaryocytic leukemia was more readily differentiated into megakaryocyte-erythroid progenitors. Whereas, the differentiation of multipotent lymphoid progenitor (MLP) and granulocyte macrophage progenitor (GMP) were blocked. The iPS derived from acute monocyte leukemia (AMCL) also showed the differentiation of common myeloid progenitors (CMP), GMP and monocytes significantly increased but MLP differentiation was inhibited. The AML-iPSC could form teratomas and we could obverse three germ layers in vivo, indicating that the AML-iPSCs have full pluripotency. However, there were not enough blood cells in teratoma to identify the leukemia. Conclusions: Our results provide a novel platform for AL research and critical insight into the difference of hematopoietic differentiation between ALL and AML.

Published in Stem Cell Research

ISSN: 1873-5061 (Print); 1876-7753 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: https://www.journals.elsevier.com/stem-cell-research

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