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Live cell detection of chromosome 2 deletion and Sfpi1/PU1 loss in radiation-induced mouse acute myeloid leukaemia.

Olme CH, Finnon R, Brown N, Kabacik S, Bouffler SD, Badie C - Leuk. Res. (2013)

Bottom Line: A specific interstitial deletion of chromosome 2 found in a high proportion of rAML is recognised as the initiating event.Although the deletion can be detected early following ionising radiation exposure by cytogenetic techniques, precise characterisation of the haematopoietic cells carrying the deletion and the study of their fate in vivo cannot be achieved.This study presents the first experimental evidence for the detection of this leukaemia initiating event in live leukemic cells.

View Article: PubMed Central - PubMed

Affiliation: Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire, UK.

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Leukaemia incidence. Kaplan–Meier analysis of cumulative probability of radiation-induced acute myeloid leukaemia in male CBA/H (total number irradiated = 57, AML induced = 9) and CBA GFP mice (total number irradiated = 100, AML induced = 18) following 3 gray acute whole body X-irradiation. For GFP AMLs, Sfpi1GFP/+ individual AMLs are represented by a white circle and Sfpi1GFP/GFP by a grey circle. No significant difference in rAML latency or penetrance was found between CBA and CBA GFP AMLs (log rank p = 0.712).
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fig0015: Leukaemia incidence. Kaplan–Meier analysis of cumulative probability of radiation-induced acute myeloid leukaemia in male CBA/H (total number irradiated = 57, AML induced = 9) and CBA GFP mice (total number irradiated = 100, AML induced = 18) following 3 gray acute whole body X-irradiation. For GFP AMLs, Sfpi1GFP/+ individual AMLs are represented by a white circle and Sfpi1GFP/GFP by a grey circle. No significant difference in rAML latency or penetrance was found between CBA and CBA GFP AMLs (log rank p = 0.712).

Mentions: In order to evaluate whether the GFP cassette would affect the incidence of rAML a total of 115 mice, 50 male Sfpi1/GFP heterozygous (Sfpi1GFP/+), 50 Sfpi1/GFP homozygous (Sfpi1GFP/GFP) and a further 15 Sfpi1GFP/GFP female mice were irradiated with 3 Gy X-rays at 12–15 weeks of age. Previous AML induction experiments within our laboratory (data unpublished) and at other institutions in the last 5 years have seen AML incidences of approximately 16% in male CBA mice. Here we report a similar incidence of 18% in male Sfpi1GFP (i.e. Sfpi1GFP/+ and Sfpi1GFP/GFP) mice, all of which arose in the same window of time; 38–89 weeks (Fig. 2). Only one female (about 7%) out of 15 was diagnosed with AML and this is consistent with previous work describing a lower incidence in CBA/H [36,37].


Live cell detection of chromosome 2 deletion and Sfpi1/PU1 loss in radiation-induced mouse acute myeloid leukaemia.

Olme CH, Finnon R, Brown N, Kabacik S, Bouffler SD, Badie C - Leuk. Res. (2013)

Leukaemia incidence. Kaplan–Meier analysis of cumulative probability of radiation-induced acute myeloid leukaemia in male CBA/H (total number irradiated = 57, AML induced = 9) and CBA GFP mice (total number irradiated = 100, AML induced = 18) following 3 gray acute whole body X-irradiation. For GFP AMLs, Sfpi1GFP/+ individual AMLs are represented by a white circle and Sfpi1GFP/GFP by a grey circle. No significant difference in rAML latency or penetrance was found between CBA and CBA GFP AMLs (log rank p = 0.712).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3775122&req=5

fig0015: Leukaemia incidence. Kaplan–Meier analysis of cumulative probability of radiation-induced acute myeloid leukaemia in male CBA/H (total number irradiated = 57, AML induced = 9) and CBA GFP mice (total number irradiated = 100, AML induced = 18) following 3 gray acute whole body X-irradiation. For GFP AMLs, Sfpi1GFP/+ individual AMLs are represented by a white circle and Sfpi1GFP/GFP by a grey circle. No significant difference in rAML latency or penetrance was found between CBA and CBA GFP AMLs (log rank p = 0.712).
Mentions: In order to evaluate whether the GFP cassette would affect the incidence of rAML a total of 115 mice, 50 male Sfpi1/GFP heterozygous (Sfpi1GFP/+), 50 Sfpi1/GFP homozygous (Sfpi1GFP/GFP) and a further 15 Sfpi1GFP/GFP female mice were irradiated with 3 Gy X-rays at 12–15 weeks of age. Previous AML induction experiments within our laboratory (data unpublished) and at other institutions in the last 5 years have seen AML incidences of approximately 16% in male CBA mice. Here we report a similar incidence of 18% in male Sfpi1GFP (i.e. Sfpi1GFP/+ and Sfpi1GFP/GFP) mice, all of which arose in the same window of time; 38–89 weeks (Fig. 2). Only one female (about 7%) out of 15 was diagnosed with AML and this is consistent with previous work describing a lower incidence in CBA/H [36,37].

Bottom Line: A specific interstitial deletion of chromosome 2 found in a high proportion of rAML is recognised as the initiating event.Although the deletion can be detected early following ionising radiation exposure by cytogenetic techniques, precise characterisation of the haematopoietic cells carrying the deletion and the study of their fate in vivo cannot be achieved.This study presents the first experimental evidence for the detection of this leukaemia initiating event in live leukemic cells.

View Article: PubMed Central - PubMed

Affiliation: Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire, UK.

Show MeSH
Related in: MedlinePlus