Distinct chromosomal abnormalities in murine leukemia virus‐induced T‐ and B‐cell lymphomas

Vasmel, W. L. E.; Matthews, E. A.; Gillis, C.; Nieland, John D.; Borst, Eric; Leupers, C. J. M.; Melief, C. J. M.; Slater, Rosalyn

doi:10.1002/ijc.2910430626

Cited by 5 publications

(6 citation statements)

References 37 publications

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“…[28][29][30][31][32] By analyzing T-cell lymphomas arising in mice with constitutional translocations involving chromosome 15, Silva et al 33 demonstrated that trisomy for bands 15D2-3 (syntenic to human 8q23-24) contributes to the development or progression (or both) of these T-cell lymphomas. This region contains the Myc and Pvt1 genes.…”

Section: Discussionmentioning

confidence: 99%

Recurring chromosomal abnormalities in leukemia inPML-RARA transgenic mice parallel human acute promyelocytic leukemia

Beau

Bitts

Davis

et al. 2002

Blood

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Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q11.2), which results in the PML-RARA fusion gene. In previous studies, we demonstrated that expression of a human PML-RARA complementary DNA in murine granulocyte precursor cells initiated the development of leukemia. However, leukemogenesis by PML-RARA required additional genetic alterations. To identify genetic changes that cooperate with PML-RARA in leukemogenesis, we performed spectral karyotyping analysis of myeloid leukemias from hMRP8-PML-RARA mice (11 cases) and from mice coexpressing PML-RARA and BCL2 (8 cases). Clonal abnormalities were detected in 18 of 19 cases (95%). Recurring numerical abnormalities identified in these murine leukemias included ؉15 (15 cases, 79%); loss of a sex chromosome (12 cases, 63%); ؉8 (10 cases, 53%); ؉10 (9 cases, 47%); ؉4, ؉7, or ؉14 (8 cases each, 42%); ؉16 (7 cases, 37%); and ؉6 (5 cases, 26%). In a series of 965 patients with APL, we identified secondary abnormalities in 368 (38%). The most common recurring abnormalities were ؉8 or partial trisomy of 8q (120 patients, 12.4%) and ider(17) t(15;17) (42 patients, 4.4%). The critical consequence of ؉8 in human leukemias appears to be the gain of 8q24, which is syntenic to mouse 15. Thus, our results suggest that PML-RARA-initiated murine leukemia is associated with a defined spectrum of genetic changes, and that these secondary mutations recapitulate, in part, the cytogenetic abnormalities found in human APL. (Blood. 2002;99:2985-2991

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Section: Discussionmentioning

confidence: 99%

Recurring chromosomal abnormalities in leukemia inPML-RARA transgenic mice parallel human acute promyelocytic leukemia

Beau

Bitts

Davis

et al. 2002

Blood

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“…Considering that M-MuLV tumors are near diploid, we conclude that there was nearly a two-fold increase in total RNA per cell in the lymphomas. [26] When adjusting for the total RNA content per cell, we find that the number of miRNAs significantly increased in lymphomas is comparable to the number that are decreased (Figure 1B). Likewise, the sum total quantity of miRNA in lymphomas was equivalent to normal tissue (Fold change = 1.08±0.05, tumor vs. normal, mean ± SE) when considered on a per cell basis.…”

Section: Resultsmentioning

confidence: 72%

Effect of Xpcl1 Activation and p27Kip1 Loss on Gene Expression in Murine Lymphoma

et al. 2011

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Mice lacking the p27Kip1 Cdk inhibitor (Cdkn1b) exhibit increased susceptibility to lymphomas from the Maloney murine leukemia virus (M-MuLV), and exhibit a high frequency of viral integrations at Xpcl1 (Kis2), a locus on the X-chromosome. Xpcl1 encodes miR-106a∼363, a cluster of microRNAs that are expressed in response to adjacent retroviral integrations. We report the first large-scale profile of microRNA expression in MuLV-induced lymphomas, in combination with microarray gene expression analysis. The source material was T-cell lymphomas induced by M-MuLV in p27Kip1 knockout mice and normal thymus. Surprisingly, the overall levels of miRNA expression were equivalent in lymphomas and normal thymus. Nonetheless, the expression of specific microRNAs was altered in tumors. The miR-106a∼363 miRNA were over-expressed in lymphomas, particularly those with viral integrations at the Xpcl1 locus. In contrast, p27Kip1 deletion itself was associated with a different pattern of microRNA expression. Gene expression was dramatically altered in lymphomas, yet paralleled data from T-cell lymphomas induced by other mechanisms. Genes with altered expression in association with the p27Kip1 null genotype were of similar functional classes to those associated with Xpcl1 integration, but with the opposite pattern of expression. Thus, the effect of p27Kip1 deletion may be to oppose an anti-oncogenic effect of Xpcl1 rather than enhancing its oncogenic functions. A subset of miR-106a∼363 target genes was consistently reduced in lymphomas with Xpcl1 integrations, particularly genes with cell cycle and immune functions. We identify four predicted target genes of miR-106a∼363 miRNA, including N-Myc (Mycn), and the TGF-beta receptor (Tgfbr2) using 3'UTR reporter assays. Still, bioinformatic miRNA target predictions were poor predictors of altered gene expression in lymphomas with Xpcl1 integration. Confirmation of miR-106a∼363 gene targeting relevant to the tumor phenotype requires in vivo validation, because only a subset of predicted targets are consistently reduced in tumors that overexpress miR-106a∼363.

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“…The accompanying report (Vasmel et al, 1989) describes the cytogenetic properties of a group of B-and T-cell lymphomas from this system. If the karyotype indicated the possibility of a translocation or other chromosomal abnormality in the vicinity of a known resident oncogene, the structure of that locus was specifically examined in that tumor.…”

Section: Southern Analysis Of Long-latency B-cell Tumorsmentioning

confidence: 99%

“…The breakpoint of the translocation t(6;16) in B-cell tumor 6 shown in Figure 2 of Vasmel et al (1989) lies in band 6C2, (Quint et al, 1984). (b) The same blot as a , probed with a p t -1 probe (Graham et al, 1985).…”

Section: Southern Analysis Of Long-latency B-cell Tumorsmentioning

confidence: 99%

“…In the accompanying paper (Vasmel et al, 1989), a karyotypic analysis of a representative group of MuLV-induced Tand B-cell lymphomas is presented. There we show that, in contrast to the relatively simple cytogenetics observed in retrovirally induced T-cell tumors, the B-cell tumors demonstrate an extremely complex series of chromosomal aberrations with no single consistent abnormality.…”

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confidence: 99%

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Retrovirally induced murine B‐cell tumors rarely show proviral integration in sites common in T‐cell tumors

Matthews

Vasmel

Schoenmakers

et al. 1989

Intl Journal of Cancer

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The molecular etiology of retrovirally induced T-cell tumors has been shown in many cases to involve proviral integration near a cellular oncogene, c-myc, N-myc, Pim-1 and pvt-1 being frequent targets for insertional activation. Murine B-cell tumors induced by infection with murine leukemia virus have been studied for rearrangements in these and other loci. In contrast to the T-cell lymphomas, tumors of the B-cell lineage, either early B-cell tumors induced in nude mice or late B-cell tumors in immunocompetent mice, did not show disruption of N-myc or Pim-1 in any of the tumors studied, although those lymphomas had acquired many new proviruses. The loci c-abl, bcl-2, fis-1, c-erbB, c-myb, and neu were likewise not involved. Rearrangement of c-myc was seen in 1 out of 71 and rearrangement of the pvt-1 locus in 4 out of 73 (5%) of the B-cell tumors. Thus it appears that mechanistic differences exist in the development of T-cell tumors and B-cell tumors caused by the same etiological agent.

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Distinct chromosomal abnormalities in murine leukemia virus‐induced T‐ and B‐cell lymphomas

Cited by 5 publications

References 37 publications

Recurring chromosomal abnormalities in leukemia inPML-RARA transgenic mice parallel human acute promyelocytic leukemia

Recurring chromosomal abnormalities in leukemia inPML-RARA transgenic mice parallel human acute promyelocytic leukemia

Effect of Xpcl1 Activation and p27Kip1 Loss on Gene Expression in Murine Lymphoma

Retrovirally induced murine B‐cell tumors rarely show proviral integration in sites common in T‐cell tumors

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