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Editorial
. 2012 Jan;97(1):5-8.
doi: 10.3324/haematol.2011.057109.

ATM and chronic lymphocytic leukemia: mutations, and not only deletions, matter

Davide Rossi, Gianluca Gaidano
Editorial

ATM and chronic lymphocytic leukemia: mutations, and not only deletions, matter

Davide Rossi et al. Haematologica. 2012 Jan.
No abstract available

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Figures

Figure 1.
Figure 1.
A proposed model of CLL multistep pathogenesis and of its clinical implications. Although the overwhelming majority of cases do not run in families, the genetic background of the host might favor predisposition to CLL in a fraction of patients. A founding genetic lesion, conceivably represented by loss of miRNA15/16 in a substantial fraction of CLL, initiates clonal expansion, that is then favored and promoted by interactions of leukemic cells with antigens and/or the microenvironment. During their clinical course, some patients gain molecular alterations of genes (TP53, ATM, NOTCH1, SF3B1, and possibly other) that confer a higher degree of clinical aggressiveness which translates into refractoriness to conventional treatments and potential of transformation to diffuse large B cell lymphoma known as Richter’s syndrome.
Figure 2.
Figure 2.
Mechanisms of ATM structural alterations in CLL. Upper panel: most CLL patients carry normal (represented by blue boxes in the figure) ATM genes in their germline DNA (A), although some cases may harbor germline mutations of ATM (represented by red boxes in the figure) (B). Lower panel: at some stage during the clinical history of the disease, CLL cells may acquire somatic alterations of ATM, alternatively constituted by: ATM deletion in the presence of a residual normal ATM allele (C); somatically acquired ATM mutations (represented by orange boxes in the figure) in the presence of a residual normal ATM allele (D); biallelic ATM inactivation through deletion of one allele and somatic mutation (represented by orange boxes in the figure) of the residual allele (E); biallelic ATM inactivation through somatically acquired deletion of one allele and germline mutation (represented by red boxes in the figure) of the other allele (G). In some cases, only a germline ATM mutation (represented by red boxes in the figure) is detected in CLL cells (F).
See this image and copyright information in PMC

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References

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