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Stability of patient-specific features of altered DNA replication timing in xenografts of primary human acute lymphoblastic leukemia.

Title: Stability of patient-specific features of altered DNA replication timing in xenografts of primary human acute lymphoblastic leukemia.
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Name(s): Sasaki, Takayo, author
Rivera-Mulia, Juan Carlos, author
Vera, Daniel, author
Zimmerman, Jared, author
Das, Sunny, author
Padget, Michelle, author
Nakamichi, Naoto, author
Chang, Bill H, author
Tyner, Jeff, author
Druker, Brian J, author
Weng, Andrew P, author
Civin, Curt I, author
Eaves, Connie J, author
Gilbert, David M, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2017-07-01
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Genome-wide DNA replication timing (RT) profiles reflect the global three-dimensional chromosome architecture of cells. They also provide a comprehensive and unique megabase-scale picture of cellular epigenetic state. Thus, normal differentiation involves reproducible changes in RT, and transformation generally perturbs these, although the potential effects of altered RT on the properties of transformed cells remain largely unknown. A major challenge to interrogating these issues in human acute lymphoid leukemia (ALL) is the low proliferative activity of most of the cells, which may be further reduced in cryopreserved samples and difficult to overcome in vitro. In contrast, the ability of many human ALL cell populations to expand when transplanted into highly immunodeficient mice is well documented. To examine the stability of DNA RT profiles of serially passaged xenografts of primary human B- and T-ALL cells, we first devised a method that circumvents the need for bromodeoxyuridine incorporation to distinguish early versus late S-phase cells. Using this and more standard protocols, we found consistently strong retention in xenografts of the original patient-specific RT features. Moreover, in a case in which genomic analyses indicated changing subclonal dynamics in serial passages, the RT profiles tracked concordantly. These results indicate that DNA RT is a relatively stable feature of human ALLs propagated in immunodeficient mice. In addition, they suggest the power of this approach for future interrogation of the origin and consequences of altered DNA RT in ALL.
Identifier: FSU_pmch_28433605 (IID), 10.1016/j.exphem.2017.04.004 (DOI), PMC5491210 (PMCID), 28433605 (RID), 28433605 (EID), S0301-472X(17)30136-4 (PII)
Grant Number: P01 GM085354, R01 GM083337, R21 CA161666
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491210.
Subject(s): Animals
Cell Proliferation
DNA Replication
DNA, Neoplasm/biosynthesis
Female
Heterografts
Humans
Male
Mice, Inbred NOD
Mice, Knockout
Mice, SCID
Neoplasm Transplantation
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/metabolism
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/metabolism
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/pathology
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_28433605
Owner Institution: FSU
Is Part Of: Experimental hematology.
1873-2399
Issue: vol. 51

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Sasaki, T., Rivera-Mulia, J. C., Vera, D., Zimmerman, J., Das, S., Padget, M., … Gilbert, D. M. (2017). Stability of patient-specific features of altered DNA replication timing in xenografts of primary human acute lymphoblastic leukemia. Experimental Hematology. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_28433605