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

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

doi:10.3324/haematol.2024.287124

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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

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).

Original language	English
Journal	Haematologica
Early online date	10 Jul 2025
DOIs	https://doi.org/10.3324/haematol.2024.287124
Publication status	E-pub ahead of print - 10 Jul 2025

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title = "PHF6 interacts with the LMO2 complex in T-cell acute lymphoblastic leukemia",

abstract = "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).",

author = "Stanulovi{\'c}, \{Vesna S.\} and Sarah Binhassan and Jaber, \{Budoor A.\} and Shimaa Alazmi and Saleman, \{Fatma M. B.\} and Sandeep Potluri and Guy Pratt and Christian Ludwig and Ward, \{Douglas G\} and Maarten Hoogenkamp",

year = "2025",

month = jul,

day = "10",

doi = "10.3324/haematol.2024.287124",

language = "English",

journal = "Haematologica",

issn = "0390-6078",

publisher = "Ferrata Storti Foundation",

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TY - JOUR

T1 - PHF6 interacts with the LMO2 complex in T-cell acute lymphoblastic leukemia

AU - Stanulović, Vesna S.

AU - Binhassan, Sarah

AU - Jaber, Budoor A.

AU - Alazmi, Shimaa

AU - Saleman, Fatma M. B.

AU - Potluri, Sandeep

AU - Pratt, Guy

AU - Ludwig, Christian

AU - Ward, Douglas G

AU - Hoogenkamp, Maarten

PY - 2025/7/10

Y1 - 2025/7/10

N2 - 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).

AB - 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).

U2 - 10.3324/haematol.2024.287124

DO - 10.3324/haematol.2024.287124

M3 - Article

C2 - 40637766

SN - 0390-6078

JO - Haematologica

JF - Haematologica

ER -

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

Abstract

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