Expression of c-myc and c-fos During Phorbol Ester Induced Differentiation of B-type Chronic Lymphocytic Leukemia Cells

Nilsson, Kenneth; Larsson, Lars‐Gunnar; Carlsson, Mats; Danersund, Antero; Forsbeck, Klas; Hellman, Lars; Tötterman, Thomas H.; Pettersson, Ulf

doi:10.1007/978-3-642-71562-4_42

Cited by 10 publications

(13 citation statements)

References 8 publications

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“…In support of this view it should be noted that c-Myc inclusions are also observed in non-transfected, cytokine-activated lymphocytes. (Heikkila et al, 1987;Larsson et al, 1991). Importantly, the nucleolar accumulation sites in our experiments are distinct from the nuclear bodies that have been observed previously since cells containing nucleolar c-Myc do not contain other sites of c-Myc accumulation (Figs 2-5).…”

Section: Discussionsupporting

confidence: 61%

Accumulation of c-Myc and proteasomes at the nucleoli of cells containing elevated c-Myc protein levels

Arabi

Rustum

Hallberg

et al. 2003

Journal of Cell Science

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c-Myc is a predominately nuclear transcription factor that is a substrate for rapid turnover by the proteasome system. Cancer-related mutations in c-Myc lead to defects in its degradation and thereby contribute to the increase in its cellular level that is associated with the disease. Little is known about the mechanisms that target c-Myc to the proteasomes. By using a GFP fusion protein and live analysis we show that c-Myc shuttles between the nucleus and cytoplasm and thus it could be degraded in either compartment. Strikingly, at elevated levels of expression c-Myc accumulates at nucleoli in some cells,consistent with saturation of a nucleolus-associated degradation system in these cells. This idea is further supported by the observation that proteasome inhibitor treatment causes accumulation of c-Myc at the nucleoli of essentially all cells. Under these conditions c-Myc is relatively stably associated with the nucleolus, as would be expected if the nucleolus functions as a sequestration/degradation site for excess c-Myc. Furthermore, during elevated c-Myc expression or proteasome inhibition, nucleoli that are associated with c-Myc also accumulate proteasomes. c-Myc and proteasomes co-localise in intranucleolar regions distinct from the dense fibrillar component of the nucleolus. Based on these results we propose a model for c-Myc downregulation where c-Myc is sequestered at the nucleoli. Sequestration of c-Myc is accompanied by recruitment of proteasomes and may lead to subsequent degradation.

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Section: Discussionsupporting

confidence: 61%

Accumulation of c-Myc and proteasomes at the nucleoli of cells containing elevated c-Myc protein levels

Arabi

Rustum

Hallberg

et al. 2003

Journal of Cell Science

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“…c-Myc downregulation, accompanied by growth arrest, has been shown to be associated with terminal differentiation in many cell lineages in addition to B cells (16,25,34,36,57). However, the precise mechanism(s) by which c-Myc functions in terminal differentiation is not well understood.…”

Section: Ectopic Expression Of C-myc Blocks Terminal Differentiation mentioning

confidence: 99%

“…For example, chromosomal translocations of the c-myc gene to Ig gene loci are present in most human Burkitt's lymphomas and murine plasmacytomas (37), and transgenic mice expressing c-myc under the control of the E heavy-chain intronic enhancer develop progressive, stage-nonrestricted B-lymphoid neoplasias (1) preceded by increased cell size of pretransformed B cells (28). Finally, c-Myc expression declines as B cells differentiate into memory cells (42) or Ig-secreting plasma cells (36). Although the importance of c-Myc for growth control during normal B lymphopoiesis and in B-cell tumors is clear, the significance, if any, of c-myc repression during terminal B-cell differentiation has not been carefully investigated.…”

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confidence: 99%

Repression of c-mycIs Necessary but Not Sufficient for Terminal Differentiation of B Lymphocytes In Vitro

Lin¹,

Lin²,

Calame

2000

Molecular and Cellular Biology

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The importance of c-myc as a target of the Blimp-1 repressor has been studied in BCL-1 cells, in which Blimp-1 is sufficient to trigger terminal B-cell differentiation. Our data show that Blimp-1-dependent repression of c-myc is required for BCL-1 differentiation, since constitutive expression of c-Myc blocked differentiation. Furthermore, ectopic expression of cyclin E mimicked the effects of c-Myc on both proliferation and differentiation, indicating that the ability of c-Myc to drive proliferation is responsible for blocking BCL-1 differentiation. However, inhibition of c-Myc by a dominant negative form was not sufficient to drive BCL-1 differentiation. Thus, during Blimp-1-dependent plasma cell differentiation, repression of c-myc is necessary but not sufficient, demonstrating the existence of additional Blimp-1 target genes.

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“…32 Yet, MYC is up-regulated by translocations in Burkitt's lymphoma and mature B cell and T cell ALL, and by amplification or other mechanisms in AML and in several solid tumors. 29,[33][34][35][36] Like ETV6 (see above), its partner in the t(12;21) translocation, AML1, was found to be over-expressed.…”

Section: Discussionmentioning

confidence: 99%

Expression of myeloid-specific genes in childhood acute lymphoblastic leukemia – a cDNA array study

et al. 2002

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Several specific cytogenetic changes are known to be associated with childhood acute lymphoblastic leukemia (ALL), and many of them are important prognostic factors for the disease. Little is known, however, about the changes in gene expression in ALL. Recently, the development of cDNA array technology has enabled the study of expression of hundreds to thousands of genes in a single experiment. We used the cDNA array method to study the gene expression profiles of 17 children with precursor-B ALL. Normal B cells from adenoids were used as reference material. We discuss the 25 genes that were most over-expressed compared to the reference. These included four genes that are normally expressed only in the myeloid lineages of the hematopoietic cells: RNASE2, GCSFR, PRTN3 and CLC. We also detected over-expression of S100A12, expressed in nerve cells but also in myeloid cells. In addition to the myeloid-specific genes, other over-expressed genes included AML1, LCP2 and FGF6. In conclusion, our study revealed novel information about gene expression in childhood ALL. The data obtained may contribute to further studies of the pathogenesis and prognosis of childhood ALL.

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Expression of c-myc and c-fos During Phorbol Ester Induced Differentiation of B-type Chronic Lymphocytic Leukemia Cells

Cited by 10 publications

References 8 publications

Accumulation of c-Myc and proteasomes at the nucleoli of cells containing elevated c-Myc protein levels

Accumulation of c-Myc and proteasomes at the nucleoli of cells containing elevated c-Myc protein levels

Repression of c-mycIs Necessary but Not Sufficient for Terminal Differentiation of B Lymphocytes In Vitro

Expression of myeloid-specific genes in childhood acute lymphoblastic leukemia – a cDNA array study

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