Alterations in TP53, cyclin D2, c-Myc, p21WAF1/CIP1 and p27KIP1 expression associated with progression in B-CLL.

Antosz, H; Artur, Paterski; Marzec-Kotarska, Barbara; Sajewicz, Joanna; Dmoszyńska, Anna

doi:10.2478/v10042-010-0048-5

Cited by 10 publications

(5 citation statements)

References 37 publications

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“…A recent report by Chang et al, gives credence to this theory since they showed that c-Myc induced expression of miR17-92 cluster and a more global repression of other microRNAs led to the development of B cell lymphomas ). An increased c-Myc transcript level is associated with disease progression and severity in CLL patients (Halina et al, 2010). Interestingly miR15a/16 expression is negatively regulated by c-Myc via repression of the Dleu2 promoter (Lerner et al, 2009).…”

Section: Potential Triggers For Regulation Of Mir15a/16 and B-1 Clonamentioning

confidence: 99%

Altering microRNA miR15a/16 Levels as Potential Therapy in CLL: Extrapolating from the De Novo NZB Mouse Model

Kasar¹,

Yao²,

Underbayev³

et al. 2012

Chronic Lymphocytic Leukemia

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Section: Potential Triggers For Regulation Of Mir15a/16 and B-1 Clonamentioning

confidence: 99%

Altering microRNA miR15a/16 Levels as Potential Therapy in CLL: Extrapolating from the De Novo NZB Mouse Model

Kasar¹,

Yao²,

Underbayev³

et al. 2012

Chronic Lymphocytic Leukemia

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“…At transformation, between 25 and 60% of RT tumors display inactivation of TP53 and ~50% acquire epigenetic changes affecting c-MYC expression, suggesting dysregulation of these pathways contribute to the pathogenesis of RT 4 – 7 . Complex karyotype, CDKN2A/B gene locus deletion, and aberrant NOTCH1 activation are also associated with RT 8 – 11 . While these discoveries contributed to the understanding of RT biology, comprehensive studies underlying CLL-to-RT progression are needed to identify patients at risk of transformation and to discover targeted therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of PRMT5 in chronic lymphocytic leukemia promotes progression with high risk of Richter’s transformation

et al. 2023

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Richter’s Transformation (RT) is a poorly understood and fatal progression of chronic lymphocytic leukemia (CLL) manifesting histologically as diffuse large B-cell lymphoma. Protein arginine methyltransferase 5 (PRMT5) is implicated in lymphomagenesis, but its role in CLL or RT progression is unknown. We demonstrate herein that tumors uniformly overexpress PRMT5 in patients with progression to RT. Furthermore, mice with B-specific overexpression of hPRMT5 develop a B-lymphoid expansion with increased risk of death, and Eµ-PRMT5/TCL1 double transgenic mice develop a highly aggressive disease with transformation that histologically resembles RT; where large-scale transcriptional profiling identifies oncogenic pathways mediating PRMT5-driven disease progression. Lastly, we report the development of a SAM-competitive PRMT5 inhibitor, PRT382, with exclusive selectivity and optimal in vitro and in vivo activity compared to available PRMT5 inhibitors. Taken together, the discovery that PRMT5 drives oncogenic pathways promoting RT provides a compelling rationale for clinical investigation of PRMT5 inhibitors such as PRT382 in aggressive CLL/RT cases.

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“…It has been reported that p53 is inactivated in 10-15% of CLL patients decreasing cell apoptosis and accelerating disease development (6). Additionally, the anti-apoptotic protein Bcl-2 family is overexpressed, while pro-apoptotic proteins such as Bax and Bcl-xL are underexpressed in CLL cells (1,7).…”

Section: Introductionmentioning

confidence: 99%

Plumbagin reduces chronic lymphocytic leukemia cell survival by downregulation of Bcl-2 but upregulation of the Bax protein level

Gong

Shi

et al. 2016

Oncology Reports

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Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, and mainly originates from an accumulation of abnormal B cells caused by the dysregulation of cell proliferation and apoptosis rates. The aberration of apoptosis-related genes in CLL cells results in defective apoptosis of CLL cells in response to traditional therapeutic medicine. Plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone), a natural compound from Plumbago zeylinica, has been shown to exhibit pro-apoptotic activities in tumor cells. In the present study, we report that plumbagin effectively inhibited CLL cell viability with a lower dose compared to fludarabine, and inhibited cell proliferation in a dose-dependent manner. In addition, plumbagin promoted accumulation of MEC-1 cells in the S phase, and blocked cell cycle transition of HG3 cells from G0/G1 to S phase. Molecularly, plumbagin markedly induced CLL cell apoptosis through reduction of Bcl-2, but through an increase in the Bax protein level. These results suggest that plumbagin may be considered as a potential anticancer agent for CLL therapy.

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Alterations in TP53, cyclin D2, c-Myc, p21WAF1/CIP1 and p27KIP1 expression associated with progression in B-CLL.

Abstract: was nearly statistically significant whereas that of p21 WAF1/CIP1 showed no such correlation. Moreover, high expression levels of TP53 and c-Myc genes were found to be closely associated with more aggressive forms of the disease requiring earlier therapy.

Cited by 10 publications

References 37 publications

Altering microRNA miR15a/16 Levels as Potential Therapy in CLL: Extrapolating from the De Novo NZB Mouse Model

Altering microRNA miR15a/16 Levels as Potential Therapy in CLL: Extrapolating from the De Novo NZB Mouse Model

Dysregulation of PRMT5 in chronic lymphocytic leukemia promotes progression with high risk of Richter’s transformation

Plumbagin reduces chronic lymphocytic leukemia cell survival by downregulation of Bcl-2 but upregulation of the Bax protein level

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