Stage-specific human induced pluripotent stem cells map the progression of myeloid transformation to transplantable leukemia Journal Article
| Authors: | Kotini, A. G.; Chang, C. J.; Chow, A.; Yuan, H.; Ho, T. C.; Wang, T.; Vora, S.; Solovyov, A.; Husser, C.; Olszewska, M.; Teruya-Feldstein, J.; Perumal, D.; Klimek, V. M.; Spyridonidis, A.; Rampal, R. K.; Silverman, L.; Reddy, E. P.; Papaemmanuil, E.; Parekh, S.; Greenbaum, B. D.; Leslie, C. S.; Kharas, M. G.; Papapetrou, E. P. |
| Article Title: | Stage-specific human induced pluripotent stem cells map the progression of myeloid transformation to transplantable leukemia |
| 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. © 2017 Elsevier Inc. |
| Keywords: | leukemia; transplantation; myelodysplastic syndrome; induced pluripotent stem cells; acute myeloid leukemia; cancer progression; hpsc-derived hematopoiesis; ipsc disease modeling; leukemia progression; myeloid malignancy |
| Journal Title: | Cell Stem Cell |
| Volume: | 20 |
| Issue: | 3 |
| ISSN: | 1934-5909 |
| Publisher: | Cell Press |
| Date Published: | 2017-03-02 |
| Start Page: | 315 |
| End Page: | 328.e7 |
| Language: | English |
| DOI: | 10.1016/j.stem.2017.01.009 |
| PROVIDER: | scopus |
| PMCID: | PMC5337161 |
| PUBMED: | 28215825 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 April 2017 -- Source: Scopus |
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