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Proliferation of primitive myeloid progenitors can be reversibly induced by HOXA10

Björnsson, Jon Mar LU ; Andersson, Elisabet ; Lundström, Patrik LU ; Larsson, Nina LU ; Xu, Xiufeng ; Repetowska, Ewa LU ; Humphries, R. Keith and Karlsson, Stefan LU orcid (2001) In Blood 98(12). p.3301-3308
Abstract
Recent studies show that several Hox transcription factors are important for regulation of proliferation and differentiation in hematopoiesis. Among these is HOXA10, which is selectively expressed at high levels in the most primitive subpopulation of human CD34(+) bone marrow cells. When overexpressed, HOXA10 increases the proliferation of early progenitor cells and can lead to the development of myeloid leukemia. To study the effects of HOXA10 on primitive hematopoietic progenitors in more detail, transgenic mice were generated with regulatable HOXA10 expression. The transgenic mouse model, referred to as tetO-HOXA10, contains the HOXA10 gene controlled by a tetracycline-responsive element and a minimal promoter. Thus, the expression of... (More)
Recent studies show that several Hox transcription factors are important for regulation of proliferation and differentiation in hematopoiesis. Among these is HOXA10, which is selectively expressed at high levels in the most primitive subpopulation of human CD34(+) bone marrow cells. When overexpressed, HOXA10 increases the proliferation of early progenitor cells and can lead to the development of myeloid leukemia. To study the effects of HOXA10 on primitive hematopoietic progenitors in more detail, transgenic mice were generated with regulatable HOXA10 expression. The transgenic mouse model, referred to as tetO-HOXA10, contains the HOXA10 gene controlled by a tetracycline-responsive element and a minimal promoter. Thus, the expression of HOXA10 is inducible and reversible depending on the absence or presence of tetracycline or its analog, doxycycline. A retroviral vector containing the tetracycline transactivator gene (tTA) was used to induce expression of the HOXA10 gene In bone marrow cells from the transgenic mice. Reverse transcription-polymerase chain reaction analysis confirmed regulatable HOXA10 expression in several transgenic lines. HOXA10 induction led to the formation of hematopoietic colonies containing blastlike cells and megakaryocytes. Moreover, the induction of HOXA10 resulted in significant proliferative advantage of primitive hematopoietic progenitors (spleen colony-forming units [CFU-S-12]), which was reversible on withdrawal of induction. Activation of HOXA10 expression in tet0-HOXA10 mice will therefore govern proliferation of primitive myeloid progenitors in a regulated fashion. This novel animal model can be used to identify the target genes of HOXA10 and better clarify, the specific role of HOXA10 in normal and malignant hematopoiesis. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
98
issue
12
pages
3301 - 3308
publisher
American Society of Hematology
external identifiers
  • wos:000172321100020
  • scopus:0035761453
ISSN
1528-0020
DOI
10.1182/blood.V98.12.3301
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Division of Molecular Medicine and Gene Therapy (013022010), Biophysical Chemistry (LTH) (011001011), Stem Cell and Pancreas Developmental Biology (013212044), Division of Clinical Genetics (013022003)
id
f2fc95d7-12a8-48c9-9091-9599279d315a (old id 1118670)
date added to LUP
2016-04-01 12:26:47
date last changed
2022-01-27 03:49:39
@article{f2fc95d7-12a8-48c9-9091-9599279d315a,
  abstract     = {{Recent studies show that several Hox transcription factors are important for regulation of proliferation and differentiation in hematopoiesis. Among these is HOXA10, which is selectively expressed at high levels in the most primitive subpopulation of human CD34(+) bone marrow cells. When overexpressed, HOXA10 increases the proliferation of early progenitor cells and can lead to the development of myeloid leukemia. To study the effects of HOXA10 on primitive hematopoietic progenitors in more detail, transgenic mice were generated with regulatable HOXA10 expression. The transgenic mouse model, referred to as tetO-HOXA10, contains the HOXA10 gene controlled by a tetracycline-responsive element and a minimal promoter. Thus, the expression of HOXA10 is inducible and reversible depending on the absence or presence of tetracycline or its analog, doxycycline. A retroviral vector containing the tetracycline transactivator gene (tTA) was used to induce expression of the HOXA10 gene In bone marrow cells from the transgenic mice. Reverse transcription-polymerase chain reaction analysis confirmed regulatable HOXA10 expression in several transgenic lines. HOXA10 induction led to the formation of hematopoietic colonies containing blastlike cells and megakaryocytes. Moreover, the induction of HOXA10 resulted in significant proliferative advantage of primitive hematopoietic progenitors (spleen colony-forming units [CFU-S-12]), which was reversible on withdrawal of induction. Activation of HOXA10 expression in tet0-HOXA10 mice will therefore govern proliferation of primitive myeloid progenitors in a regulated fashion. This novel animal model can be used to identify the target genes of HOXA10 and better clarify, the specific role of HOXA10 in normal and malignant hematopoiesis.}},
  author       = {{Björnsson, Jon Mar and Andersson, Elisabet and Lundström, Patrik and Larsson, Nina and Xu, Xiufeng and Repetowska, Ewa and Humphries, R. Keith and Karlsson, Stefan}},
  issn         = {{1528-0020}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{3301--3308}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood}},
  title        = {{Proliferation of primitive myeloid progenitors can be reversibly induced by HOXA10}},
  url          = {{http://dx.doi.org/10.1182/blood.V98.12.3301}},
  doi          = {{10.1182/blood.V98.12.3301}},
  volume       = {{98}},
  year         = {{2001}},
}