to 23 abnormalities were found in less than 5 percent of cases. The minimally deleted region contains a number of candidate tumor suppressor genes, including RDX, which has homology to the neurofibromatosis type 2 gene (NF2 71); PPP2RIB, a phosphatase which is mutated in sporadic cases of lung and colon cancer; and ATM, which is mutated in ataxia telangecta-sia. The ATM gene encodes a 350-kd protein, which has roles in stress response, cell cycle regulation, and DNA repair. Patients with ataxia telangiectasia are prone to a variety of T- and B-cell tumors, although rarely CLL.

Mutation of the PPP2RIB gene or loss of phosphatase activity has not been found in cases of CLL with deletion of one copy of the PPP2RIB gene.30 In contrast two studies have shown reduced expression of the ATM protein in 34 and 40 percent of cases of CLL, respectively.31 Several groups have identified mutations within the ATM gene, particularly in patients with 11q23 deletions.32,33 In two studies germ-line ATM mutations were found, raising the possibility that carriers of ATM mutations may be at risk of developing CLL. Schaffner et al.34 detected ATM mutations in only 5 of 22 patients with 11q deletions. Although the whole of the ATM gene was not analyzed, cases of mantle-cell lymphoma with deletion of 11q all involved mutation of the remaining ATM allele, which suggests that other genes situated in 11q may be important in CLL.35


Chromosomal deletions or translocations involving chromosome 17p are found in 1 to 5 percent of patients with CLL. In a recent study using FISH, 10 out of 14 patients with 17p translocations were shown to have dicentric rearrangements36 (Figure 6-3). The p53 gene is located at 17p13, and numerous studies (Table 6-3) using a variety of techniques (including single-strand confirmation polymorphism analysis, genomic sequencing, FISH, and p53 protein expression using immunocytochemistry or flow cytometry) have shown p53 mutation or deletion in 7 to 30 percent of patients with CLL. The varying incidence is partly technical but largely reflects the clinical stage of the patients being studied. Patients with deletion of 17p13 frequently have a mutation of the remaining allele. Mutations of the p53 gene are usually missense mutations involving exons 4 to 8, although rarely genomic deletions have been identified.37

The p53 gene encodes a DNA-binding protein that induces the expression of genes such as p21, involved in cell cycle arrest, and BAX, which is proapoptotic. The regulation of functional p53 protein is complex and is shown in a highly simplified form in Figure 6-4. Failure to upregulate p21 expression following in vitro irradiation appears to identify cases with either p53 or ATM mutations.38 The p53 gene induces the expression of MDM2, which inactivates p53 in a variety of ways including tl

How To Deal With Rosacea and Eczema

How To Deal With Rosacea and Eczema

Rosacea and Eczema are two skin conditions that are fairly commonly found throughout the world. Each of them is characterized by different features, and can be both discomfiting as well as result in undesirable appearance features. In a nutshell, theyre problems that many would want to deal with.

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