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Replication timing alterations in leukemia affect clinically relevant chromosome domains
- Source :
- Blood Advances, Vol 3, Iss 21, Pp 3201-3213 (2019)
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
Abstract
- Abstract: Human B-cell precursor acute lymphoid leukemias (BCP-ALLs) comprise a group of genetically and clinically distinct disease entities with features of differentiation arrest at known stages of normal B-lineage differentiation. We previously showed that BCP-ALL cells display unique and clonally heritable, stable DNA replication timing (RT) programs (ie, programs describing the variable order of replication and subnuclear 3D architecture of megabase-scale chromosomal units of DNA in different cell types). To determine the extent to which BCP-ALL RT programs mirror or deviate from specific stages of normal human B-cell differentiation, we transplanted immunodeficient mice with quiescent normal human CD34+ cord blood cells and obtained RT signatures of the regenerating B-lineage populations. We then compared these with RT signatures for leukemic cells from a large cohort of BCP-ALL patients with varied genetic subtypes and outcomes. The results identify BCP-ALL subtype-specific features that resemble specific stages of B-cell differentiation and features that seem to be associated with relapse. These results suggest that the genesis of BCP-ALL involves alterations in RT that reflect biologically significant and potentially clinically relevant leukemia-specific epigenetic changes.
- Subjects :
- Specialties of internal medicine
RC581-951
Subjects
Details
- Language :
- English
- ISSN :
- 24739529 and 54453364
- Volume :
- 3
- Issue :
- 21
- Database :
- Directory of Open Access Journals
- Journal :
- Blood Advances
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.813e5445336443a09e50cbf90d7c35a2
- Document Type :
- article
- Full Text :
- https://doi.org/10.1182/bloodadvances.2019000641