B-lineage transcription factors and cooperating gene lesions required for leukemia development

Tijchon, Esther; Havinga, Jørn; Leeuwen, Frank N. van; Scheijen, Blanca

doi:10.1038/leu.2012.293

Cited by 71 publications

(55 citation statements)

References 145 publications

(202 reference statements)

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“…PCNSLs also had mutations of BTG1 (43% [6/14]) and TBL1XR1 (36% [5/14]), transcriptional cofactors that regulate ETV6 activity ( Figure 4A and supplemental Figure 7D). 51 Of interest, TBL1XR1 also modulates TLR/MYD88 signaling by increasing clearance of NCor/SMRT transcriptional corepressors from certain TLR/MYD88 target genes. 52 …”

Section: Recurrent Somatic Mutations In Pcnslmentioning

confidence: 99%

Targetable genetic features of primary testicular and primary central nervous system lymphomas

Chapuy

Roemer

Stewart

et al. 2016

Blood

484

450

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Section: Recurrent Somatic Mutations In Pcnslmentioning

confidence: 99%

Targetable genetic features of primary testicular and primary central nervous system lymphomas

Chapuy

Roemer

Stewart

et al. 2016

Blood

484

450

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“…Aberrant expression of various transcription factors can predispose developing B cells to leukemia (2). Development of B cell progenitors requires signaling through the IL-7R (3,4).…”

mentioning

confidence: 99%

PU.1 Opposes IL-7–Dependent Proliferation of Developing B Cells with Involvement of the Direct Target Gene Bruton Tyrosine Kinase

Christie

Turkistany

et al. 2015

The Journal of Immunology

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Deletion of genes encoding the E26 transformation-specific transcription factors PU.1 and Spi-B in B cells (CD19-CreΔPB mice) leads to impaired B cell development, followed by B cell acute lymphoblastic leukemia at 100% incidence and with a median survival of 21 wk. However, little is known about the target genes that explain leukemogenesis in these mice. In this study we found that immature B cells were altered in frequency in the bone marrow of preleukemic CD19-CreΔPB mice. Enriched pro–B cells from CD19-CreΔPB mice induced disease upon transplantation, suggesting that these were leukemia-initiating cells. Bone marrow cells from preleukemic CD19-CreΔPB mice had increased responsiveness to IL-7 and could proliferate indefinitely in response to this cytokine. Bruton tyrosine kinase (BTK), a negative regulator of IL-7 signaling, was reduced in preleukemic and leukemic CD19-CreΔPB cells compared with controls. Induction of PU.1 expression in cultured CD19-CreΔPB pro–B cell lines induced Btk expression, followed by reduced STAT5 phosphorylation and early apoptosis. PU.1 and Spi-B regulated Btk directly as shown by chromatin immunoprecipitation analysis. Ectopic expression of BTK was sufficient to induce apoptosis in cultured pro–B cells. In summary, these results suggest that PU.1 and Spi-B activate Btk to oppose IL-7 responsiveness in developing B cells.

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“…BTG1 and TBL1XR1 deletions have been described only in B precursor ALL and not in T cell ALL, thus far (6,8,28,41,42). This suggests that distinct biological mechanisms may be utilized by the different cell types for acquiring steroid resistance.…”

Section: Discussionmentioning

confidence: 99%

Loss of TBL1XR1 Disrupts Glucocorticoid Receptor Recruitment to Chromatin and Results in Glucocorticoid Resistance in a B-Lymphoblastic Leukemia Model

Jones

Bhatla

Blum

et al. 2014

Journal of Biological Chemistry

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Background:Resistance to glucocorticoid agonists is a major challenge in the treatment of pediatric leukemia. Results: TBL1XR1 knockdown decreases glucocorticoid signaling and response in leukemia cells. Conclusion:Deletions in TBL1XR1 at relapse may drive resistance to glucocorticoid agonists. Significance: Identifying drivers of glucocorticoid resistance in leukemia may allow for the identification of novel therapies for the treatment of recurrent disease.

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B-lineage transcription factors and cooperating gene lesions required for leukemia development

Cited by 71 publications

References 145 publications

Targetable genetic features of primary testicular and primary central nervous system lymphomas

Targetable genetic features of primary testicular and primary central nervous system lymphomas

PU.1 Opposes IL-7–Dependent Proliferation of Developing B Cells with Involvement of the Direct Target Gene Bruton Tyrosine Kinase

Loss of TBL1XR1 Disrupts Glucocorticoid Receptor Recruitment to Chromatin and Results in Glucocorticoid Resistance in a B-Lymphoblastic Leukemia Model

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