MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies

Ahmadi, Seyed Esmaeil; Rostom, S.; Zarandi, Bahman; Chegeni, Rouzbeh; Safa, Majid

doi:10.1186/s13045-021-01111-4

Cited by 81 publications

(32 citation statements)

References 754 publications

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“…Genomic instability is one of the key drivers of hematological malignancy and is responsible for leukemia progression [ 38 ]. Genomic instability, including mutations in DNA sequences, chromosomal aneuploidy, translocations, and gene amplifications, are frequently found in leukemia cells suggesting that the DSB response may be altered.…”

Section: Introductionmentioning

confidence: 99%

Involvement of classic and alternative non-homologous end joining pathways in hematologic malignancies: targeting strategies for treatment

et al. 2021

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Chromosomal translocations are the main etiological factor of hematologic malignancies. These translocations are generally the consequence of aberrant DNA double-strand break (DSB) repair. DSBs arise either exogenously or endogenously in cells and are repaired by major pathways, including non-homologous end-joining (NHEJ), homologous recombination (HR), and other minor pathways such as alternative end-joining (A-EJ). Therefore, defective NHEJ, HR, or A-EJ pathways force hematopoietic cells toward tumorigenesis. As some components of these repair pathways are overactivated in various tumor entities, targeting these pathways in cancer cells can sensitize them, especially resistant clones, to radiation or chemotherapy agents. However, targeted therapy-based studies are currently underway in this area, and furtherly there are some biological pitfalls, clinical issues, and limitations related to these targeted therapies, which need to be considered. This review aimed to investigate the alteration of DNA repair elements of C-NHEJ and A-EJ in hematologic malignancies and evaluate the potential targeted therapies against these pathways.

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Section: Introductionmentioning

confidence: 99%

Involvement of classic and alternative non-homologous end joining pathways in hematologic malignancies: targeting strategies for treatment

et al. 2021

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“…With this setting, GSEA disclosed that, in comparison with the sole blockade of either RSK2 or AKT, the combination of blockade in the two kinases proved more powerful effects on several critical gene sets involved in myeloma pathophysiologies, such as those associated with MYC, mTOR, STK33, ribosomal biogenesis, or cell-extrinsic stimuli of soluble factors. MYC is a multifunctional oncogenic transcription factor that affects various cell biological processes, including cell proliferation, apoptosis, and DNA damage in various cancerous diseases, including myeloma [ 44 , 45 ]. Furthermore, MYC is frequently overexpressed through various overlapping mechanisms, such as cytogenetic, epigenetic, and IRF4-mediated transcriptional mechanisms, in myeloma cells, and plays critical roles in cell survival and proliferation of myeloma cells, thereby constituting the fundamental process in both the development and progression of MM [ 45 , 46 , 47 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

The Rationale for the Dual-Targeting Therapy for RSK2 and AKT in Multiple Myeloma

Isa

Horinaka

Tsukamoto

et al. 2022

IJMS

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Multiple myeloma (MM) is characterized by remarkable cytogenetic/molecular heterogeneity among patients and intraclonal diversity even in a single patient. We previously demonstrated that PDPK1, the master kinase of series of AGC kinases, is universally active in MM, and plays pivotal roles in cell proliferation and cell survival of myeloma cells regardless of the profiles of cytogenetic and genetic abnormalities. This study investigated the therapeutic efficacy and mechanism of action of dual blockade of two major PDPK1 substrates, RSK2 and AKT, in MM. The combinatory treatment of BI-D1870, an inhibitor for N-terminal kinase domain (NTKD) of RSK2, and ipatasertib, an inhibitor for AKT, showed the additive to synergistic anti-tumor effect on human MM-derived cell lines (HMCLs) with active RSK2-NTKD and AKT, by enhancing apoptotic induction with BIM and BID activation. Moreover, the dual blockade of RSK2 and AKT exerted robust molecular effects on critical gene sets associated with myeloma pathophysiologies, such as those with MYC, mTOR, STK33, ribosomal biogenesis, or cell-extrinsic stimuli of soluble factors, in HMCLs. These results provide the biological and molecular rationales for the dual-targeting strategy for RSK2 and AKT, which may overcome the therapeutic difficulty due to cytogenetic/molecular heterogeneity in MM.

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“…The original article [ 1 ] incorrectly states that OMO-1 is a MYC inhibitor in two instances: in the Direct MYC Inhibition sub-section of the MYC Inhibitors section, and in Table 3.…”

Section: Correction To: J Hematol Oncol (2021) 14:121 101186/s13045-021-01111-4mentioning

confidence: 99%

Correction to: MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies

et al. 2021

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MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies

Cited by 81 publications

References 754 publications

Involvement of classic and alternative non-homologous end joining pathways in hematologic malignancies: targeting strategies for treatment

Involvement of classic and alternative non-homologous end joining pathways in hematologic malignancies: targeting strategies for treatment

The Rationale for the Dual-Targeting Therapy for RSK2 and AKT in Multiple Myeloma

Correction to: MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies

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