PHF6 interacts with the LMO2 complex in T-cell acute lymphoblastic leukemia

The transcriptional mediator LIM domain only 2 (LMO2) forms a large multi-protein complex together with TAL1/LYL1, HEB/E2A, LDB1 and GATA. This complex regulates transcription from the onset of hematopoietic development and during differentiation. Chromosomal rearrangements involving LMO2 and TAL1...

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Main Authors: Vesna S. Stanulović, Sarah Binhassan, Budoor A. Jaber, Shimaa Alazmi, Fatma M.B. Saleman, Sandeep Potluri, Guy Pratt, Christian Ludwig, Douglas G. Ward, Maarten Hoogenkamp
Format: Article
Language:English
Published: Ferrata Storti Foundation 2025-07-01
Series:Haematologica
Online Access:https://haematologica.org/article/view/12167
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author Vesna S. Stanulović
Sarah Binhassan
Budoor A. Jaber
Shimaa Alazmi
Fatma M.B. Saleman
Sandeep Potluri
Guy Pratt
Christian Ludwig
Douglas G. Ward
Maarten Hoogenkamp
author_facet Vesna S. Stanulović
Sarah Binhassan
Budoor A. Jaber
Shimaa Alazmi
Fatma M.B. Saleman
Sandeep Potluri
Guy Pratt
Christian Ludwig
Douglas G. Ward
Maarten Hoogenkamp
author_sort Vesna S. Stanulović
collection DOAJ
description The transcriptional mediator LIM domain only 2 (LMO2) forms a large multi-protein complex together with TAL1/LYL1, HEB/E2A, LDB1 and GATA. This complex regulates transcription from the onset of hematopoietic development and during differentiation. Chromosomal rearrangements involving LMO2 and TAL1 are causative for T-cell lymphoblastic leukemia (TALL). We have identified Plant Homeodomain (PHD)-like Finger 6 (PHF6) as a new LMO2 interacting factor. Somatic mutations in PHF6 have been found to occur in several types of leukemia. We show that PHF6 interacts with LMO2 as a part of the TAL1, GATA2, LDB1 complex in T-ALL and binds to the DNA. These findings show that PHF6 associates with the TAL1/LMO2/LDB1/GATA2 complex and regulates genes that have a major role in blood development, such as SPI1 (PU.1).
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institution OA Journals
issn 0390-6078
1592-8721
language English
publishDate 2025-07-01
publisher Ferrata Storti Foundation
record_format Article
series Haematologica
spelling doaj-art-9d06280a019f42a3a229e0362f96a5bf2025-08-20T02:36:03ZengFerrata Storti FoundationHaematologica0390-60781592-87212025-07-01999110.3324/haematol.2024.287124PHF6 interacts with the LMO2 complex in T-cell acute lymphoblastic leukemiaVesna S. Stanulović0Sarah Binhassan1Budoor A. Jaber2Shimaa Alazmi3Fatma M.B. Saleman4Sandeep Potluri5Guy Pratt6Christian Ludwig7Douglas G. Ward8Maarten Hoogenkamp9Department of Cancer and Genomics Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, United Kingdom; Birmingham Centre for Genome Biology, University of Birmingham, Birmingham B15 2TTDepartment of Cancer and Genomics Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, United Kingdom; Birmingham Centre for Genome Biology, University of Birmingham, Birmingham B15 2TTDepartment of Cancer and Genomics Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham B15 2TTDepartment of Cancer and Genomics Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, United Kingdom; Birmingham Centre for Genome Biology, University of Birmingham, Birmingham B15 2TTDepartment of Cancer and Genomics Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, United Kingdom; Birmingham Centre for Genome Biology, University of Birmingham, Birmingham B15 2TTDepartment of Cancer and Genomics Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, United Kingdom; Birmingham Centre for Genome Biology, University of Birmingham, Birmingham B15 2TTDepartment of Cancer and Genomics Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, United Kingdom; Centre for Clinical Haematology, Queen Elizabeth Hospital Birmingham, BirminghamDepartment of Metabolism and Systems Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham B15 2TTDepartment of Cancer and Genomics Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham B15 2TTDepartment of Cancer and Genomics Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, United Kingdom; Birmingham Centre for Genome Biology, University of Birmingham, Birmingham B15 2TT The transcriptional mediator LIM domain only 2 (LMO2) forms a large multi-protein complex together with TAL1/LYL1, HEB/E2A, LDB1 and GATA. This complex regulates transcription from the onset of hematopoietic development and during differentiation. Chromosomal rearrangements involving LMO2 and TAL1 are causative for T-cell lymphoblastic leukemia (TALL). We have identified Plant Homeodomain (PHD)-like Finger 6 (PHF6) as a new LMO2 interacting factor. Somatic mutations in PHF6 have been found to occur in several types of leukemia. We show that PHF6 interacts with LMO2 as a part of the TAL1, GATA2, LDB1 complex in T-ALL and binds to the DNA. These findings show that PHF6 associates with the TAL1/LMO2/LDB1/GATA2 complex and regulates genes that have a major role in blood development, such as SPI1 (PU.1). https://haematologica.org/article/view/12167
spellingShingle Vesna S. Stanulović
Sarah Binhassan
Budoor A. Jaber
Shimaa Alazmi
Fatma M.B. Saleman
Sandeep Potluri
Guy Pratt
Christian Ludwig
Douglas G. Ward
Maarten Hoogenkamp
PHF6 interacts with the LMO2 complex in T-cell acute lymphoblastic leukemia
Haematologica
title PHF6 interacts with the LMO2 complex in T-cell acute lymphoblastic leukemia
title_full PHF6 interacts with the LMO2 complex in T-cell acute lymphoblastic leukemia
title_fullStr PHF6 interacts with the LMO2 complex in T-cell acute lymphoblastic leukemia
title_full_unstemmed PHF6 interacts with the LMO2 complex in T-cell acute lymphoblastic leukemia
title_short PHF6 interacts with the LMO2 complex in T-cell acute lymphoblastic leukemia
title_sort phf6 interacts with the lmo2 complex in t cell acute lymphoblastic leukemia
url https://haematologica.org/article/view/12167
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