In:
eLife, eLife Sciences Publications, Ltd, Vol. 2 ( 2013-07-16)
Kurzfassung:
Blood cells are produced within bone marrow by specialized stem cells and progenitor cells. Abnormalities in this process lead to a group of diseases known as myeloid malignancies, which include acute myeloid leukaemia—in which the bone marrow produces abnormal white blood cells—and myelodysplastic syndromes, which are caused by too few mature blood cells being produced. Many individuals affected by these disorders possess a shortened form of chromosome 20 that lacks a number of genes. This deletion is only ever seen in one of their two copies of the chromosome—suggesting that at least some of these genes are essential for survival—but the identity of the gene(s) that are associated with the increased risk of myeloid malignancies is unknown. Now, Heinrichs et al. have uncovered a key tumor suppressor among those genes frequently lost on chromosome 20. The gene, which is called MYBL2 , encodes a transcription factor that helps to control the cell division cycle. Myeloid malignancy patients lacking one copy of this gene showed levels of MYBL2 expression that were less than 50% of those in healthy individuals. This suggests that additional mechanisms must be acting to reduce expression of their remaining copy of the gene. Surprisingly, MYBL2 levels were also reduced in myeloid malignancy patients who possessed two intact copies of chromosome 20, indicating that loss of a single copy represents only one mechanism to reduce MYBL2 expression, i.e., the ‘tip-of-the-iceberg’. Hence, this finding reveals a more general role for MYBL2 as it indicates that more patients are likely to be affected by altered expression of this gene. To confirm their findings from studies in patients, Heinrichs et al. used gene silencing techniques to reduce the expression of MYBL2 in mice and showed that this induced symptoms of myeloid malignancies in the animals. Moreover, injection of modified cells from these animals into healthy mice also induced symptoms in the recipients. The modified cells are able to expand more robustly than normal cells, and this dominance induced by downregulation of the tumor suppressor increases the risk of malignancy. In addition to revealing a new tumor suppressor gene and its contribution to myeloid malignancies, the study by Heinrichs et al. highlights the importance of gene dosage in mediating the effects of tumor suppressors.
Materialart:
Online-Ressource
ISSN:
2050-084X
DOI:
10.7554/eLife.00825.001
DOI:
10.7554/eLife.00825.002
DOI:
10.7554/eLife.00825.003
DOI:
10.7554/eLife.00825.004
DOI:
10.7554/eLife.00825.005
DOI:
10.7554/eLife.00825.006
DOI:
10.7554/eLife.00825.007
DOI:
10.7554/eLife.00825.008
DOI:
10.7554/eLife.00825.009
DOI:
10.7554/eLife.00825.010
DOI:
10.7554/eLife.00825.011
DOI:
10.7554/eLife.00825.012
DOI:
10.7554/eLife.00825.013
DOI:
10.7554/eLife.00825.014
DOI:
10.7554/eLife.00825.015
DOI:
10.7554/eLife.00825.016
DOI:
10.7554/eLife.00825.017
DOI:
10.7554/eLife.00825.018
DOI:
10.7554/eLife.00825.019
DOI:
10.7554/eLife.00825.020
DOI:
10.7554/eLife.00825.021
DOI:
10.7554/eLife.00825.022
DOI:
10.7554/eLife.00825.023
DOI:
10.7554/eLife.00825.024
DOI:
10.7554/eLife.00825.025
DOI:
10.7554/eLife.00825.026
Sprache:
Englisch
Verlag:
eLife Sciences Publications, Ltd
Publikationsdatum:
2013
ZDB Id:
2687154-3
