Ibrutinib in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma: A Retrospective Study

Ren, Liangliang; Li, Ling; Zhang, Lei; Li, Xin; Fu, Xiaorui; Wang, Xinhua; Wu, Jingjing; Sun, Zhenchang; Feng, Xiaoyan; Chang, Yu; Zhou, Zhiyuan; Nan, Feifei; Yan, Jiaqin; Kong, Fei; Zhang, Mingzhi

doi:10.1007/s12288-021-01433-w

Cited by 3 publications

(2 citation statements)

References 32 publications

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“… 50 A study about the treatment of DLBCL with ibrutinib revealed that a combination with other drugs such as lenalidomide leads to markedly better prognosis. 51 For the treatment of BL, it might be beneficial to combine the inhibition of tonic BCR survival signals, such as PI3K, with SHIP protein inhibition. Because of its ubiquitous expression, inhibition of SHIP2 might cause more side effects than the inhibition of SHIP1, which is mainly found in cells of hematopoietic origin.…”

Section: Discussionmentioning

confidence: 99%

SH2 domain-containing inositol 5-phosphatases support the survival of Burkitt lymphoma cells by promoting energy metabolism

Mayr,

Kruse,

Fuhrmann

et al. 2023

haematol

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Burkitt lymphoma cells (BL) exploit antigen-independent tonic signals transduced by the B cell antigen receptor (BCR) for their survival, but the molecular details of the rewired BLspecific BCR signal network remain unclear. A loss of function screen revealed the SH2 domain-containing 5`-inositol phosphatase 2 (SHIP2) as a potential modulator of BL fitness. We characterized the role of SHIP2 in BL survival in several BL cell models and show that perturbing SHIP2 function renders cells more susceptible to apoptosis, while attenuating proliferation in a BCR-dependent manner. Unexpectedly, SHIP2 deficiency did neither affect PI3K survival signals nor MAPK activity, but attenuated ATP production. We found that an efficient energy metabolism in BL cells requires phosphatidylinositol-3,4-bisphosphate (PI(3,4)P2), which is the enzymatic product of SHIP proteins. Consistently, interference with the function of SHIP1 and SHIP2 augments BL cell susceptibility to PI3K inhibition. Notably, we here provide a molecular basis of how tonic BCR signals are connected to energy supply, which is particularly important for such an aggressively growing neoplasia. These findings may help to improve therapies for the treatment of BL by limiting energy metabolism through the inhibition of SHIP proteins, which renders BL cells more susceptible to the targeting of survival signals.

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Section: Discussionmentioning

confidence: 99%

SH2 domain-containing inositol 5-phosphatases support the survival of Burkitt lymphoma cells by promoting energy metabolism

Mayr,

Kruse,

Fuhrmann

et al. 2023

haematol

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“…Abnormal activation of BTK-regulated BCR signaling pathway was reported as an important driver of the pathogenesis of DL-CBL 10) . As an irreversible inhibitor of BTK, ibrutinib plays an anti-cancer role in diverse B-cell malignancies, especially DLBCL 11,12) . In spite of the positive role of ibrutinib in DLBCL treatment, drug resistance hinders its effectiveness 13) .…”

Section: Introductionmentioning

confidence: 99%

Upregulation of miR-101-3p Overcomes Ibrutinib Resistance by Targeting ABCC5 in Diffuse Large B-Cell Lymphoma (DLBCL)

Liu

Gao

et al. 2023

J. Hard Tissue Biology.

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Diffuse large B-cell lymphoma (DLBCL) seriously threatens public health, and drug resistance is a formidable obstacle to DLBCL therapy. MicroRNAs (miRNAs) have been certified to act as a momentous regulator in drug resistance of DLBCL. This study aimed to ascertain the latent function and mechanism of miR-101-3p in modulating the resistance of DLBCL cells to ibrutinib. The differentially expressed miRNAs were identified by bioinformatics analysis of GSE117063 and GSE173080 datasets. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to measure the expression levels of miR-101-3p and ATP-binding cassette subfamily C member 5 (ABCC5). The resistance of DLBCL cells to ibrutinib was determined by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and Western blot assays. The relationship between miR-101-3p expression level and ABCC5 expression level was analyzed using dual-luciferase reporter assay and Pearson correlation test. MiR-101-3p was significantly downregulated in DLBCL cells according to the results of the bioinformatics analysis. A low miR-101-3p expression level predicted resistance of DL-BCL cells to ibrutinib. Upregulation of miR-101-3p sensitized the constructed ibrutinib-resistant DLBCL (DLBCL/ibR). Our findings revealed that ABCC5 was targeted by miR-101-3p, and ABCC5 was abundantly expressed in DLBCL/ibR tissue samples and cells. Furthermore, miR-101-3p mimics overturned the influences of ABCC5 upregulation on the resistance of DLBCL cells to ibrutinib. MiR-101-3p played a suppressive function in the resistance of DLBCL cells to ibrutinib via inhibiting ABCC5 expression, which might represent a potent therapeutic target for DLBCL.

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Ibrutinib/lenalidomide/rituximab

2023

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Ibrutinib in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma: A Retrospective Study

Cited by 3 publications

References 32 publications

SH2 domain-containing inositol 5-phosphatases support the survival of Burkitt lymphoma cells by promoting energy metabolism

SH2 domain-containing inositol 5-phosphatases support the survival of Burkitt lymphoma cells by promoting energy metabolism

Upregulation of miR-101-3p Overcomes Ibrutinib Resistance by Targeting ABCC5 in Diffuse Large B-Cell Lymphoma (DLBCL)

Ibrutinib/lenalidomide/rituximab

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