Evidence for clustered tumour suppressor gene loci on mouse chromosomes 2 and 4 in radiation-induced Acute Myeloid Leukaemia

Jawad, Mays; Cole, Clare; Zanker, Abigail; Lo, Priscilla; Fitch, Simon R.; Plumb, Mark

doi:10.1080/09553000600784161

Cited by 9 publications

(6 citation statements)

References 29 publications

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“…Mouse chromosome 2 aberrations have been linked to development of radiation-induced AML (37-39). Interestingly, mouse chromosome 2 contains clustered tumor suppressor gene loci and Pu.1 gene (40).…”

Section: Discussionmentioning

confidence: 99%

Disruption of NAD(P)H:Quinone Oxidoreductase 1 Gene in Mice Leads to Radiation-Induced Myeloproliferative Disease

2008

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Section: Discussionmentioning

confidence: 99%

Disruption of NAD(P)H:Quinone Oxidoreductase 1 Gene in Mice Leads to Radiation-Induced Myeloproliferative Disease

2008

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“…Similarly, a susceptibility to pristane-induced plasmacytoma QTL has been mapped to a position on chromosome 1 (54 cM) (Mock et al 1993) that is very similar to QTL that determine the frequency of L -S + K + cells (~65 cM; Table 3), the frequency of bone marrow LTC-IC cells (~50 cM) (Muller-Sieburg and Riblet 1996) and the relative proportion of B220 B lymphocytes in mouse peripheral blood (Pbbcp1; 62-64 cM) (Chen and Harrison 2002). Similarly a QTL that confers a susceptibility to radiation-induced AML was mapped to distal chromosome 1 (~100 cM; Boulton et al 2003;Jawad et al 2006), a position that is very similar to the Scfr1 locus (~100 cM) that also determines the frequency of LTC-IC bone marrow cells (Muller-Sieburg and Riblet 1996). However, the distal chromosome 1 LTC-IC QTL was not revealed in this study, suggesting that the colonies in the LTC-IC clonogenic assay are phenotypically heterogeneous.…”

Section: Discussionmentioning

confidence: 86%

QTL analyses of lineage-negative mouse bone marrow cells labeled with Sca-1 and c-Kit

et al. 2008

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Differences in the number of functionally and/or phenotypically defined bone marrow cells in inbred mouse strains have been exploited to map quantitative trait loci (QTL) that determine the variation in cell frequency. To extend this approach to the differences in the stem/progenitor cell compartment in CBA/H and C57BL/6 mice, we have exploited the resolution of flow cytometry and the power of QTL analyses in 124 F2 mice to analyse lineage negative (Lin -) bone marrow cells according to the intensity of labelling with Sca-1 and c-Kit. In the Lin -Sca-1 + c-Kit + enriched population six quantitative trait loci (QTL) were identified -one significant and five suggestive. Whereas previous in vitro clonogenic, LTIC-IC, CAFC day 35, and flow cytometry each identified different QTL, our approach identified the same or very similar QTL at all three loci (Chromosome 1, 17 and 18) as well as QTL on chromosomes 6 and 10. In silico analyses implicate haematopoietic stem cell homing involving Cxcr4 and Cxcl12 as being the determining pathway. The mapping of the same or very similar QTLs in independent studies using different assay(s) suggests a common genetic determinant, and thus reinforces the biological and genetic significance of the QTL. These data also suggest that mouse bone marrow cell subpopulations can be functionally, phenotypically and genetically defined.3

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“…This technique can be useful for understanding radiation leukemogenesis. The partial deletion of chromosome 2 by radiation is suspected to be an initiating event of radiation leukemogenesis [ 9 ]. FISH analysis using blood smears can use living mice so that the time course of chromosomal changes can be surveyed for individuals during leukemogenesis.…”

Section: Resultsmentioning

confidence: 99%

Rapid and reliable diagnosis of murine myeloid leukemia (ML) by FISH of peripheral blood smear using probe of PU. 1, a candidate ML tumor suppressor

Kanda¹,

Tsuji²,

Ohmachi³

et al. 2008

Mol Cytogenet

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BackgroundMurine myeloid leukemia (ML) provides a good animal model to study the mechanisms of radiation-induced leukemia in humans. This disease has been cytogenetically characterized by a partial deletion of chromosome 2 with G-banding. For the rapid diagnosis of ML, this study reports a FISH method using spleen cells and peripheral blood smears from ML mice exposed to gamma rays and neutrons with PU.1, a candidate ML tumor suppressor, as a probe.ResultsAmong mice that were tentatively diagnosed with ML by clinical findings and blood smear examination, 85% carried spleen cells showing the loss of PU.1 although the frequency of these abnormal cells varied among individuals. Mice with very low frequencies of cells showing the loss of one copy of PU.1 (one-PU.1 frequency) were later diagnosed pathologically not with ML but with blastic or eosinophilic leukemia. Some neutron-irradiated mice had cells showing translocated PU.1, although no pathological features differentiated these ML mice from ML mice expressing the simple loss of PU.1.The one-PU.1 frequency can be detected from spleen metaphase cells, spleen interphase cells, and blood smears. There was a good correlation between the one-PU.1 frequency in spleen metaphase cells and that in spleen interphase cells (r = 0.96) and between one-PU.1 frequency in spleen interphase cells and that in blood cells (r = 0.83).ConclusionThe FISH method was capable of detecting aberration of copy number of the PU.1 gene on murine chromosome 2, and using a peripheral blood smear is more practical and less invasive than conventional pathological diagnosis or the cytogenetic examination of spleen cells.

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Evidence for clustered tumour suppressor gene loci on mouse chromosomes 2 and 4 in radiation-induced Acute Myeloid Leukaemia

Abstract: Allelic loss in mouse r-AML and subsequent tumour suppressor gene mutation (PU1) or silencing (Pax5) is strongly influenced by genetic background and/or epigenetic factors, and driven by in vivo clonal selection.

Cited by 9 publications

References 29 publications

Disruption of NAD(P)H:Quinone Oxidoreductase 1 Gene in Mice Leads to Radiation-Induced Myeloproliferative Disease

Disruption of NAD(P)H:Quinone Oxidoreductase 1 Gene in Mice Leads to Radiation-Induced Myeloproliferative Disease

QTL analyses of lineage-negative mouse bone marrow cells labeled with Sca-1 and c-Kit

Rapid and reliable diagnosis of murine myeloid leukemia (ML) by FISH of peripheral blood smear using probe of PU. 1, a candidate ML tumor suppressor

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