MYC antagonizes the differentiation induced by imatinib in chronic myeloid leukemia cells through downregulation of p27KIP1

Gómez-Casares, M T; García-Alegría, Eva; López-Jorge, C E; Ferrándiz, Nuria; Blanco, Raquel; Álvarez, Sara; Vaqué, José P.; Bretones, Gabriel; Caraballo, Juan M.; Sánchez-Bailón, P; Delgado, M. Dolores; Martı́n-Pérez, Jorge; Cigudosa, Juan C.; León, Javier

doi:10.1038/onc.2012.246

Cited by 55 publications

(52 citation statements)

References 43 publications

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“…cDNAs preparation by reverse transcription and quantitative polymerase chain reaction (RT-qPCR) was performed as described previously (40). The primers for the assayed genes are shown in Table 2.…”

Section: Breast Tumor Samples and Immunohistochemical Analysis-mentioning

confidence: 99%

Sin3b Interacts with Myc and Decreases Myc Levels

García-Sanz

Quintanilla

Lafita

et al. 2014

Journal of Biological Chemistry

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Background: Myc is an oncogenic transcription factor that is frequently deregulated in cancer, and Sin3b is a transcriptional regulator that recruits histone deacetylases. Results: A new interaction between the protein Sin3b and Myc that leads to Myc down-regulation is described. Conclusion: Sin3b-Myc interaction regulates Myc levels and activity. Significance: Sin3b adds a second level of control of Myc by directly regulating Myc levels.

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Section: Breast Tumor Samples and Immunohistochemical Analysis-mentioning

confidence: 99%

Sin3b Interacts with Myc and Decreases Myc Levels

García-Sanz

Quintanilla

Lafita

et al. 2014

Journal of Biological Chemistry

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“…c-Myc is an oncogenic transcription factor, and it is found deregulated in about half of human tumors and appears frequently associated with tumor progression in solid tumors and leukemia (43,44). One of the most relevant activities of c-Myc in carcinogenesis is the impairment of cell differentiation (45), and repression of c-myc is required for terminal differentiation of many cell types, including myeloid cells (46,47). Recently, we have presented an essential role for c-Myc suppression in the differentiation-inducing effects of prostratin as a PKC activator (19).…”

Section: Discussionmentioning

confidence: 99%

Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation

Yu¹,

He²,

Wang³

et al. 2016

Cancer Research

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All-trans retinoic acid (ATRA)-based cell differentiation therapy has been successful in treating acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia (AML). However, other subtypes of AML display resistance to ATRAbased treatment. In this study, we screened natural, plantderived vibsane-type diterpenoids for their ability to induce differentiation of myeloid leukemia cells, discovering that vibsanin A potently induced differentiation of AML cell lines and primary blasts. The differentiation-inducing activity of vibsanin A was mediated through direct interaction with and activation of protein kinase C (PKC). Consistent with these findings, pharmacological blockade of PKC activity suppressed vibsanin A-induced differentiation. Mechanistically, vibsanin A-mediated activation of PKC led to induction of the ERK pathway and decreased c-Myc expression. In mouse xenograft models of AML, vibsanin A administration prolonged host survival and inhibited PKC-mediated inflammatory responses correlated with promotion of skin tumors in mice. Collectively, our results offer a preclinical proof of concept for vibsanin A as a myeloid differentiation-inducing compound, with potential application as an antileukemic agent. Cancer Res; 76(9);

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“…Consistently, imatinib and other BCR-ABL inhibitors provoke downregulation of MYC. [76][77][78][79] MYC mRNA levels are elevated in CML-blastic crisis 80,81 and in chronic phase CML compared to healthy bone marrow samples. [81][82][83] Our laboratory showed that MYC is upregulated during CML progression.…”

Section: Chronic Myeloid Leukemiamentioning

confidence: 99%

“…81 High MYC expression correlates with poorer response to imatinib and progression to blastic crisis. 81,84 MYC also induces genetic instability and blocks erythroid differentiation mediated by imatinib in CML-derived cells 77,81 suggesting that MYC contributes to CML by acting at least at those two levels.…”

Section: Chronic Myeloid Leukemiamentioning

confidence: 99%

MYC as therapeutic target in leukemia and lymphoma

Cortiguera¹,

Batlle-López²,

Albajar³

et al. 2015

BLCTT

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MYC is a transcription factor that is involved in the expression of many genes. Deregulated MYC is found in about half of human tumors, being more prevalent in hematological neoplasms. Deregulation mechanisms include chromosomal translocation (particularly in lymphoma), amplification, and hyperactivation of MYC transcription. Here we review MYC involvement in the major types of leukemia and lymphoma. MYC rearrangements appear in all Burkitt lymphomas and are common in other lymphoma types, whereas in acute lymphoblastic leukemia, acute myeloid leukemia, lymphoproliferative, and myeloproferative diseases, they are less frequent. However, MYC overexpression is present in all types of hematological malignancies and often correlates with a worse prognosis. Data in leukemia-derived cells and in animal models of lymphomagenesis and leukemogenesis suggest that MYC would be a good therapeutic target. Several MYC-directed therapies have been assayed in preclinical settings and even in clinical trials. First, peptides and small molecules that interrupt the MYC-MAX interaction impair MYCmediated tumorogenesis in several mouse models of solid tumors, although not yet in lymphoma and leukemia models. Second, there are a number of small molecules inhibiting the interaction of MYC-MAX heterodimers with DNA, still in the preclinical research phase. Third, inhibitors of MYC expression via the inhibition of BRD4 (a reader of acetylated histones) have been shown to control the growth of MYC-transformed leukemia and lymphoma cells and are being used in clinic trials. Finally, we review a number of promising MYC-mediated synthetic lethal approaches that are under study and have been tested in hematopoietic neoplasms.

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MYC antagonizes the differentiation induced by imatinib in chronic myeloid leukemia cells through downregulation of p27KIP1

Cited by 55 publications

References 43 publications

Sin3b Interacts with Myc and Decreases Myc Levels

Sin3b Interacts with Myc and Decreases Myc Levels

Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation

MYC as therapeutic target in leukemia and lymphoma

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