MYC is not overexpressed in a case of chronic myelomonocytic leukemia with MYC-containing double minutes

Paulsson, Kajsa; Lassen, Carin; Kuric, Nevzeta; Billström, Rolf; Fioretos, Thoas; Hj, Tanke; Johansson, Bertil

doi:10.1038/sj.leu.2402841

Cited by 12 publications

(6 citation statements)

References 8 publications

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“…[106][107][108] Double minute chromosomes and homogeneously staining regions containing amplified segments from chromosome band 8q24, including the MYC gene, have also been described. 106,109 However, it has been reported that a high MYC copy number does not result in higher c-Myc expression, 110,111 a situation that seems to conflict with the correlation between MYC amplification and expression observed in lymphoma. 112 MYC expression appeared elevated in a microarray-based study in 5 AML samples, as validated by RT-PCR.…”

Section: C-myc In Human Myeloid Leukemiamentioning

confidence: 99%

Myc Roles in Hematopoiesis and Leukemia

Delgado¹,

2010

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Hematopoiesis is a process capable of generating millions of cells every second, as distributed in many cell types. The process is regulated by a number of transcription factors that regulate the differentiation along the distinct lineages and dictate the genetic program that defines each mature phenotype. Myc was first discovered as the oncogene of avian leukemogenic retroviruses; it was later found translocated in human lymphoma. From then on, evidence accumulated showing that c-Myc is one of the transcription factors playing a major role in hematopoiesis. The study of genetically modified mice with overexpression or deletion of Myc has shown that c-Myc is required for the correct balance between self-renewal and differentiation of hematopoietic stem cells (HSCs). Enforced Myc expression in mice leads to reduced HSC pools owing to loss of self-renewal activity at the expense of increased proliferation of progenitor cells and differentiation. c-Myc deficiency consistently results in the accumulation of HSCs. Other models with conditional Myc deletion have demonstrated that different lineages of hematopoietic cells differ in their requirement for c-Myc to regulate their proliferation and differentiation. When transgenic mice overexpress c-Myc or N-Myc in mature cells from the lymphoid or myeloid lineages, the result is lymphoma or leukemia. In agreement, enforced expression of c-Myc blocks the differentiation in several leukemia-derived cell lines capable of differentiating in culture. Not surprising, MYC deregulation is recurrently found in many types of human lymphoma and leukemia. Whereas MYC is deregulated by translocation in Burkitt lymphoma and, less frequently, other types of lymphoma, MYC is frequently overexpressed in acute lymphoblastic and myeloid leukemia, through mechanisms unrelated to chromosomal translocation, and is often associated with disease progression.

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Section: C-myc In Human Myeloid Leukemiamentioning

confidence: 99%

Myc Roles in Hematopoiesis and Leukemia

Delgado¹,

2010

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“…MYC amplification in dmins or HSRs is often part of a complex karyotype in AML. Only a few reported cases had dmins as a sole genetic abnormality (11). The mechanism of MYC amplification in dmins or HSRs in AML has been proposed to occur by excision from an intact chromosome 8q24, circularization, and amplification by mutual recombination (12).…”

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confidence: 99%

MYC amplification in multiple marker chromosomes and EZH2 microdeletion in a man with acute myeloid leukemia

et al. 2015

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“…Amplified cancer-associated genes are often upregulated as a direct consequence of their copy number (CN) gain [ 11 ]. Nevertheless, MYC , as well as other 8q24 co-amplified genes and long noncoding RNAs (lncRNAs) (e.g., TRIB1 , FAM84B , POU5F1B , PVT1 , and TMEM75 ), represents a clear exception to this rule in myeloid malignancies [ 9 , 12 , 13 ]. These findings suggest that none of them could be considered as the real target for this type of amplification [ 14 ].…”

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confidence: 99%

MYC-containing amplicons in acute myeloid leukemia: genomic structures, evolution, and transcriptional consequences

et al. 2018

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Double minutes (dmin), homogeneously staining regions, and ring chromosomes are vehicles of gene amplification in cancer. The underlying mechanism leading to their formation as well as their structure and function in acute myeloid leukemia (AML) remain mysterious. We combined a range of high-resolution genomic methods to investigate the architecture and expression pattern of amplicons involving chromosome band 8q24 in 23 cases of AML (AML-amp). This revealed that different MYC-dmin architectures can coexist within the same leukemic cell population, indicating a step-wise evolution rather than a single event origin, such as through chromothripsis. This was supported also by the analysis of the chromothripsis criteria, that poorly matched the model in our samples. Furthermore, we found that dmin could evolve toward ring chromosomes stabilized by neocentromeres. Surprisingly, amplified genes (mainly PVT1) frequently participated in fusion transcripts lacking a corresponding DNA template. We also detected a significant overexpression of the circular RNA of PVT1 (circPVT1) in AML-amp cases versus AML with a normal karyotype. Our results show that 8q24 amplicons in AML are surprisingly plastic DNA structures with an unexpected association to novel fusion transcripts and circular RNAs.

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MYC is not overexpressed in a case of chronic myelomonocytic leukemia with MYC-containing double minutes

Cited by 12 publications

References 8 publications

Myc Roles in Hematopoiesis and Leukemia

Myc Roles in Hematopoiesis and Leukemia

MYC amplification in multiple marker chromosomes and EZH2 microdeletion in a man with acute myeloid leukemia

MYC-containing amplicons in acute myeloid leukemia: genomic structures, evolution, and transcriptional consequences

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