Trisomy 8 in human hematologic neoplasia and the c-myc and c-mos oncogenes

Dı́az, Manuel O.; Beau, Michelle M. Le; Harden, Alanna M.; Rowley, Janet D.

doi:10.1016/0145-2126(85)90033-5

Cited by 18 publications

(11 citation statements)

References 25 publications

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“…Over-expression of c-myc has been described for immortalized tumor cell lines, while c-myc down-regulation in these cells often leads to differentiation. [29][30][31][32] This observation suggests that selection of a small AML subset may strongly bias the results obtained.…”

Section: Discussionmentioning

confidence: 99%

True

1999

Leukemia

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Recently, in-frame internal tandem duplications have been reported within the regions coding for the juxtamembrane through the first tyrosine kinase domain of the Flt3 gene. These duplications have been reported to lead to autophosphorylation of the receptor. In this study we investigated the effect of such mutations in the Flt3 gene on the in vitro proliferation of human acute myeloid leukemia cells. The mutations were detected in 10 out of 59 AML bone marrow samples analyzed and were not restricted to a specific FAB class or cytogenetic aberration. PCR analysis of those samples showed all mutations to be present in exon 11 of the gene. Whilst samples without a mutation of the Flt3 gene showed an increased cell production in response to either IL-3 and G-CSF or IL-6, SCF, TPO and Flt3L in long-term stroma supported cultures, mutant samples failed to do so. As we could not find a relationship between the absence of a response and either FAB class or cytogenetic aberrations, we interpret these results as an indication that the internal tandem duplications in the Flt3 gene are the prime cause of this unresponsiveness. Although our study does not explain the mechanism by which these mutations cause this unresponsiveness it does suggest that AML cells need a wild-type Flt3 for optimal in vitro proliferation.

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Section: Discussionmentioning

confidence: 99%

True

1999

Leukemia

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“…In contrast, c-src is not involved in those with 2%- [61]. Obviously there are extra copies of c-myc and c-myb in trisomy 8, but rearrangements are uncommon [62].…”

Section: Dnamentioning

confidence: 94%

“…Several surveys of mRNA expression in human leukemias have been reported [62,[72][73][74][75][76][77][78][79][80][81]. These studies involve leukemia cell lines as well as fresh leukemia cells.…”

Section: Rnamentioning

confidence: 99%

“…Similarly, differentiation of leukemia cell lines by compounds such as phorbol esters, dimethylsulfoxide (DMSO), retinoids and others results in decreased transcription of c-myc, c-myb and c-abl, and increased transcription offos andfms. These changes appear temporally related to the development of a differentiated cell phenotype [62,[89][90][91][92][93].…”

Section: Rnamentioning

confidence: 99%

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Oncogenes and human leukemias

Butturini¹,

Gale

1988

The International Journal of Cell Cloning

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Abstract. Eukaryotic cells contain a family of genes termed "cellular oncogenes" or "proto-oncogenes," thought to regulate normal cell growth and development. In some circumstances, such as following transduction by retroviruses, activation of these genes causes tumors and leukemias in animals. Possible mechanisms of cellular oncogene activation include: 1) DNA point mutation, deletion or insertion, 2) gene amplification, 3) gene activation by internal rearrangement, chromosomal translocation or promoter insertion, 4) recombinative events resulting in the formation of novel chimeric genes, and others.

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“…Interestingly, the patient with C/EBP␣ mutation had an additional copy of chromosome 8, the locus of the c-myc gene. 23 At relapse, the clone with trisomy 8 was still present raising the possibility that this clone acquired the mutation.…”

Section: Figurementioning

confidence: 99%

The emergence of a C/EBPα mutation in the clonal evolution of MDS towards secondary AML

et al. 2003

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Recently, mutations in the transcription factor CCAAT/ enhancer binding protein alpha (C/EBP␣) have been described in acute myeloid leukemia (AML). We performed a mutational analysis of the C/EBP␣ gene in the myelodysplastic syndromes and AML with antecedent MDS. No mutations were found in patients with refractory anemia (0/27), refractory anemia with ringed sideroblasts (0/7), refractory anemia with excess of blasts (RAEB 0/16) or chronic myelomonocytic leukemia (CMML 0/5). One out of 13 patients with RAEB-T/AML secondary to MDS showed a mutation in the C/EBP␣ gene. In this patient a 4 bp insertion disrupted codon 69 in one allele. This novel +1 frame shift is predicted to result in a truncated protein of 107 amino acids. However, the dominant protein translated was the C/EBP␣ isoform p30, which was previously shown to inhibit the DNA-binding and transactivation properties of C/EBP␣ p42. Interestingly this mutation could not be detected at diagnosis in the initial RAEB and RAEB-T stage. The mutation appeared at relapse after chemotherapy for RAEB-T. We conclude that the C/EBP␣ mutation was not essential for the initial blast accumulation. The emergence of a bast clone carrying a C/EBP␣ mutation at relapse indicates that this mutation may confer a growth advantage in a myeloid cell with an established differentiation block.

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Trisomy 8 in human hematologic neoplasia and the c-myc and c-mos oncogenes

Cited by 18 publications

References 25 publications

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Oncogenes and human leukemias

The emergence of a C/EBPα mutation in the clonal evolution of MDS towards secondary AML

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