“Double-Hit” Chronic Lymphocytic Leukemia, Involving the TP53 and MYC Genes

Nguyen‐Khac, Florence

doi:10.3389/fonc.2021.826245

Cited by 4 publications

(3 citation statements)

References 28 publications

(51 reference statements)

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“…However, it is crucial to note that existing studies are primarily retrospective cohorts, with most patients already undergoing treatment. Therefore, it is imperative to conduct further assessments of the TP53 mutational status to ascertain whether the poor prognosis is indeed a consequence of the combination of a TP53mut and not only del(17p) with a MYC aberration [ 21 ].…”

Section: Pathogenesismentioning

confidence: 99%

Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era

Sánchez Suárez,

Martín Roldán,

Alarcón-Payer

et al. 2023

Pharmaceutics

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Chronic lymphocytic leukemia is a lymphoproliferative disorder marked by the expansion of monoclonal, mature CD5+CD23+ B cells in peripheral blood, secondary lymphoid tissues, and bone marrow. The disease exhibits significant heterogeneity, with numerous somatic genetic alterations identified in the neoplastic clone, notably mutated TP53 and immunoglobulin heavy chain mutational statuses. Recent studies emphasize the pivotal roles of genetics and patient fragility in treatment decisions. This complexity underscores the need for a personalized approach, tailoring interventions to individual genetic profiles for heightened efficacy. The era of personalized treatment in CLL signifies a transformative shift, holding the potential for improved outcomes in the conquest of this intricate hematologic disorder. This review plays a role in elucidating the evolving CLL treatment landscape, encompassing all reported genetic factors. Through a comprehensive historical analysis, it provides insights into the evolution of CLL management. Beyond its retrospective nature, this review could be a valuable resource for clinicians, researchers, and stakeholders, offering a window into the latest advancements. In essence, it serves as a dynamic exploration of our current position and the promising prospects on the horizon.

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Section: Pathogenesismentioning

confidence: 99%

Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era

Sánchez Suárez,

Martín Roldán,

Alarcón-Payer

et al. 2023

Pharmaceutics

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“…MYC oncogenic activation alone is usually not enough to induce neoplastic transformation. It has long been known that the loss of checkpoint proteins, such as p53 and PTEN, in parallel with MYC deregulation, contributes to the inability of the tumor cells to switch off MYC-driven metabolism and enforces cell expansion independent of growth factors and nutrient availability [ 46 , 47 , 48 , 131 , 132 ]. Similarly, since signaling pathways converge in MYC, for example, the overactivation of growth factor or mTOR signaling causes the upregulation of MYC and its modulated processes [ 42 , 43 , 44 , 45 , 131 ].…”

Section: Oncogenic Deregulation Of Myc and Its Effect On Cancer Metab...mentioning

confidence: 99%

Rewired Metabolism Caused by the Oncogenic Deregulation of MYC as an Attractive Therapeutic Target in Cancers

Vízkeleti

Spisák

2023

Cells

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MYC is one of the most deregulated oncogenes on multiple levels in cancer. As a node transcription factor, MYC plays a diverse regulatory role in many cellular processes, including cell cycle and metabolism, both in physiological and pathological conditions. The relentless growth and proliferation of tumor cells lead to an insatiable demand for energy and nutrients, which requires the rewiring of cellular metabolism. As MYC can orchestrate all aspects of cellular metabolism, its altered regulation plays a central role in these processes, such as the Warburg effect, and is a well-established hallmark of cancer development. However, our current knowledge of MYC suggests that its spatial- and concentration-dependent contribution to tumorigenesis depends more on changes in the global or relative expression of target genes. As the direct targeting of MYC is proven to be challenging due to its relatively high toxicity, understanding its underlying regulatory mechanisms is essential for the development of tumor-selective targeted therapies. The aim of this review is to comprehensively summarize the diverse forms of MYC oncogenic deregulation, including DNA-, transcriptional- and post-translational level alterations, and their consequences for cellular metabolism. Furthermore, we also review the currently available and potentially attractive therapeutic options that exploit the vulnerability arising from the metabolic rearrangement of MYC-driven tumors.

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“…Although very rare, the translocation of the MYC proto-oncogene is also observed in CLL, mostly in association with the del 17p. MYC overexpression and TP53 deletion in these so-called 'Double-Hit' CLL are extremely high-risk in nature (reviewed in [35]).…”

Section: Classification Of Cll-factors Affecting the Cll Prognosismentioning

confidence: 99%

Immunoglobulin Gene Sequence as an Inherited and Acquired Risk Factor for Chronic Lymphocytic Leukemia

Datta

Jumaa

2022

Cancers

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Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease characterized by the accumulation of CD5+ CD19+ malignant B cells. Autonomous ligand-independent B-cell signaling is a key process involved in the development of CLL pathogenesis. Together with other cytogenetic alterations, mutations in the immunoglobulin heavy chain variable (IGHV) gene act as a prognostic marker for CLL, with mutated CLL (M-CLL) being far more indolent than unmutated CLL (U-CLL). Recent studies highlight the role of a specific light chain mutation, namely, IGLV3-21R110G, in the development and prognosis of CLL. Such a mutation increases the propensity of homotypic BCR–BCR interaction, leading to cell autonomous signaling. In this article, we review the current findings on immunoglobulin gene sequence mutations as a potential risk factor for developing CLL.

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“Double-Hit” Chronic Lymphocytic Leukemia, Involving the TP53 and MYC Genes

Cited by 4 publications

References 28 publications

Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era

Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era

Rewired Metabolism Caused by the Oncogenic Deregulation of MYC as an Attractive Therapeutic Target in Cancers

Immunoglobulin Gene Sequence as an Inherited and Acquired Risk Factor for Chronic Lymphocytic Leukemia

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