Transcription factor networks link B-lymphocyte development and malignant transformation in leukemia
(2023) In Genes and Development 37(15-16). p.703-723- Abstract
Rapid advances in genomics have opened unprecedented possibilities to explore the mutational landscapes in malignant diseases, such as B-cell acute lymphoblastic leukemia (B-ALL). This disease is manifested as a severe defect in the production of normal blood cells due to the uncontrolled expansion of transformed B-lymphocyte progenitors in the bone marrow. Even though classical genetics identified translocations of transcription factor-coding genes in B-ALL, the extent of the targeting of regulatory networks in malignant transformation was not evident until the emergence of large-scale genomic analyses. There is now evidence that many B-ALL cases present with mutations in genes that encode transcription factors with critical roles in... (More)
Rapid advances in genomics have opened unprecedented possibilities to explore the mutational landscapes in malignant diseases, such as B-cell acute lymphoblastic leukemia (B-ALL). This disease is manifested as a severe defect in the production of normal blood cells due to the uncontrolled expansion of transformed B-lymphocyte progenitors in the bone marrow. Even though classical genetics identified translocations of transcription factor-coding genes in B-ALL, the extent of the targeting of regulatory networks in malignant transformation was not evident until the emergence of large-scale genomic analyses. There is now evidence that many B-ALL cases present with mutations in genes that encode transcription factors with critical roles in normal B-lymphocyte development. These include PAX5, IKZF1, EBF1, and TCF3, all of which are targeted by translocations or, more commonly, partial inactivation in cases of B-ALL. Even though there is support for the notion that germline polymorphisms in the PAX5 and IKZF1 genes predispose for B-ALL, the majority of leukemias present with somatic mutations in transcription factor-encoding genes. These genetic aberrations are often found in combination with mutations in genes that encode components of the preB-cell receptor or the IL-7/TSLP signaling pathways, all of which are important for early B-cell development. This review provides an overview of our current understanding of the molecular interplay that occurs between transcription factors and signaling events during normal and malignant B-lymphocyte development.
(Less)
- author
- Sigvardsson, Mikael LU
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- B-ALL, B-lymphocytes, transcription factors]
- in
- Genes and Development
- volume
- 37
- issue
- 15-16
- pages
- 21 pages
- publisher
- Cold Spring Harbor Laboratory Press (CSHL)
- external identifiers
-
- pmid:37673459
- scopus:85171900073
- ISSN
- 0890-9369
- DOI
- 10.1101/gad.349879.122
- language
- English
- LU publication?
- yes
- id
- 951436c9-48a8-44ba-8b45-48b75753864e
- date added to LUP
- 2023-12-19 14:07:39
- date last changed
- 2024-04-18 00:28:43
@article{951436c9-48a8-44ba-8b45-48b75753864e,
abstract = {{<p>Rapid advances in genomics have opened unprecedented possibilities to explore the mutational landscapes in malignant diseases, such as B-cell acute lymphoblastic leukemia (B-ALL). This disease is manifested as a severe defect in the production of normal blood cells due to the uncontrolled expansion of transformed B-lymphocyte progenitors in the bone marrow. Even though classical genetics identified translocations of transcription factor-coding genes in B-ALL, the extent of the targeting of regulatory networks in malignant transformation was not evident until the emergence of large-scale genomic analyses. There is now evidence that many B-ALL cases present with mutations in genes that encode transcription factors with critical roles in normal B-lymphocyte development. These include PAX5, IKZF1, EBF1, and TCF3, all of which are targeted by translocations or, more commonly, partial inactivation in cases of B-ALL. Even though there is support for the notion that germline polymorphisms in the PAX5 and IKZF1 genes predispose for B-ALL, the majority of leukemias present with somatic mutations in transcription factor-encoding genes. These genetic aberrations are often found in combination with mutations in genes that encode components of the preB-cell receptor or the IL-7/TSLP signaling pathways, all of which are important for early B-cell development. This review provides an overview of our current understanding of the molecular interplay that occurs between transcription factors and signaling events during normal and malignant B-lymphocyte development.</p>}},
author = {{Sigvardsson, Mikael}},
issn = {{0890-9369}},
keywords = {{B-ALL; B-lymphocytes; transcription factors]}},
language = {{eng}},
number = {{15-16}},
pages = {{703--723}},
publisher = {{Cold Spring Harbor Laboratory Press (CSHL)}},
series = {{Genes and Development}},
title = {{Transcription factor networks link B-lymphocyte development and malignant transformation in leukemia}},
url = {{http://dx.doi.org/10.1101/gad.349879.122}},
doi = {{10.1101/gad.349879.122}},
volume = {{37}},
year = {{2023}},
}