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Editorial
Introduction to the review series on transcription factors in
hematopoiesis and hematologic disease
In this issue of Blood is a set of 6 reviews focusing on hematopoietic
transcription factors. Transcription factors are DNA-binding proteins that initiate and regulate the activity of genes.1 At present, the
Encyclopedia of DNA Elements (ENCODE) project has described
the genome-wide occupancy of more than 150 such proteins, a subset
of which have specific roles in normal and malignant hematopoiesis.2 Previously, the topic of hematopoietic transcription factors has
been covered in comprehensive reviews that provide an overview of
the roles of many different factors, or in focused, in-depth reviews of
a single transcription factor. We recruited 6 reviews on 4 different
transcription factors to create this review series. We believe that this
series of reviews provides the readers of Blood with comprehensive information, while at the same time giving an in-depth look
at individual transcription factors and their roles in normal and malignant hematopoiesis.
Transcription factors are pleiotropic, often having different roles
in different cells at different stages of development or differentiation.
This is perhaps best exemplified by the transcription factor SCL/
TAL. The review provided by Porcher and colleagues3 highlights the
requirement for SCL/TAL for the specification of mesoderm and
eventually hematopoietic cells during development. Once hematopoiesis has begun, SCL/TAL interacts with other transcription
factors to promote differentiation in maturing myeloid cells, whereas
dysregulated expression of SCL/TAL leads to T-cell acute lymphoblastic leukemia. The central role of transcription factors in normal
hematopoiesis and their altered expression or activity in hematologic
malignancies is a recurring theme in this review series.
One of the 3 members of the RUNX family of transcription factors,
RUNX1 is required for the emergence of definitive hematopoietic stem
cells during development and for normal stem cell function. The review
by de Bruijn and Dzierzak4 traces the fundamental observations of
RUNX function in normal developmental hematopoiesis and how
RUNX1 performs multiple functions. The companion review by Sood
and colleagues5 covers the role of RUNX factors in hematologic disease,
which ranges from germ line mutations that cause familial platelet
disorder with associated myeloid malignancies to acquired mutations
that cause acute myeloid leukemia (AML) and many other disorders.
Although SCL/TAL and RUNX affect the most primitive hematopoietic cells, other transcription factors are expressed and function
mainly in specific hematopoietic lineages. The review by Avellino and
Delwel6 focuses on the myeloid transcription factor, C/EPBa. In
normal hematopoiesis, C/EPBa expression promotes myeloid differentiation and is critical for neutrophil maturation. An exciting aspect of
this review is the mechanistic explanation of how C/EPBa expression
can be altered by mutations in the CEBPA gene as well as by other
oncogenes to cause AML.
The GATA factors are a 6-member family of transcription factors
with distinct roles at specific stages of development and in specific
tissues. The review by Katsumura and Bresnick7 covers the basic
biology of the GATA factors, ranging from how they interact with
DNA to how GATA1 and GATA2 replace each other during
hematopoietic differentiation. A highlight of this review is the focus
on the interaction of GATA1 with cofactors and chromatin remodeling
proteins to execute its many functions during erythropoiesis. The
companion review by Crispino and Horwitz8 focuses on hematopoietic disorders that are associated with mutations in GATA1 and
GATA2. Given that we are beginning to understand the pleiotropic and
overlapping roles of the GATA factors in hematopoiesis, it should
come as no surprise that acquired and inherited GATA mutations are
associated with diverse clinical manifestations, including DiamondBlackfan anemia, acute megakaryoblastic leukemia, and congenital
dyserythropoietic anemia with thrombocytopenia (GATA1), as well as
myelodysplastic syndromes, AML, and blast crisis transformation in
chronic myeloid leukemia (GATA2). Together these reviews highlight
the fast-moving field of transcription factor biology that is reshaping
our understanding of normal and malignant hematology.
David M. Bodine
Associate Editor, Blood
References
1. Maston GA, Evans SK, Green MR. Transcriptional regulatory elements in the
human genome. Annu Rev Genomics Hum Genet. 2006;7:29-59.
2. Wang J, Zhuang J, Iyer S, et al. Sequence features and chromatin structure
around the genomic regions bound by 119 human transcription factors. Genome
Res. 2012;22(9):1798-1812.
3. Porcher C, Chagraoui H, Kristiansen MS. SCL/TAL1: a multifaceted regulator
from blood development to disease. Blood. 2017;129(15):2051-2060.
4. de Bruijn M, Dzierzak E. Runx transcription factors in the development and
function of the definitive hematopoietic system. Blood. 2017;129(15):2061-2069.
5. Sood R, Kamikubo Y, Liu P. Role of RUNX1 in hematological malignancies.
Blood. 2017;129(15):2070-2082.
6. Avellino R, Delwel R. Expression and regulation of C/EBPa in normal
myelopoiesis and in malignant transformation. Blood. 2017;129(15):2083-2091.
7. Katsumura KR, Bresnick EH; GATA Factor Mechanisms Group. The GATA
factor revolution in hematology. Blood. 2017;129(15):2092-2102.
8. Crispino JD, Horwitz MS. GATA factor mutations in hematologic disease. Blood.
2017;129(15):2103-2110.
Submitted 3 February 2017; accepted 4 February 2017. Prepublished online
as Blood First Edition paper, 8 February 2017; DOI 10.1182/blood-2017-02766840.
BLOOD, 13 APRIL 2017 x VOLUME 129, NUMBER 15
2039
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
2017 129: 2039
doi:10.1182/blood-2017-02-766840 originally published
online February 8, 2017
Introduction to the review series on transcription factors in
hematopoiesis and hematologic disease
David M. Bodine
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