The genetics of human hematopoiesis and its disruption in disease.

Autor: Bao EL; Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Harvard-MIT Health Sciences and Technology, Harvard Medical School, Boston, MA, USA., Cheng AN; Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Sankaran VG; Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Harvard Stem Cell Institute, Cambridge, MA, USA.
Jazyk: angličtina
Zdroj: EMBO molecular medicine [EMBO Mol Med] 2019 Aug; Vol. 11 (8), pp. e10316. Date of Electronic Publication: 2019 Jul 17.
DOI: 10.15252/emmm.201910316
Abstrakt: Hematopoiesis, or the process of blood cell production, is a paradigm of multi-lineage cellular differentiation that has been extensively studied, yet in many aspects remains incompletely understood. Nearly all clinically measured hematopoietic traits exhibit extensive variation and are highly heritable, underscoring the importance of genetic variation in these processes. This review explores how human genetics have illuminated our understanding of hematopoiesis in health and disease. The study of rare mutations in blood and immune disorders has elucidated novel roles for regulators of hematopoiesis and uncovered numerous important molecular pathways, as seen through examples such as Diamond-Blackfan anemia and the GATA2 deficiency syndromes. Additionally, population studies of common genetic variation have revealed mechanisms by which human hematopoiesis can be modulated. We discuss advances in functionally characterizing common variants associated with blood cell traits and discuss therapeutic insights, such as the discovery of BCL11A as a modulator of fetal hemoglobin expression. Finally, as genetic techniques continue to evolve, we discuss the prospects, challenges, and unanswered questions that lie ahead in this burgeoning field.
(© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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