ATM mutations in B-cell chronic lymphocytic leukemia.
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Bullrich F, Rasio D, Kitada S, Starostik P, Kipps T, Keating M, Albitar M, Reed JC, Croce CM
ATM mutations in B-cell chronic lymphocytic leukemia.
Cancer Res. 1999 Jan 1;59(1):24-7.
- PubMed ID
- 9892178 [ View in PubMed]
- Abstract
Mutations in the ATM gene located on the long arm of chromosome 11 at 11q22-23 cause ataxia-telangiectasia, an autosomal recessive disorder that is associated with increased incidence of malignancy and, particularly, lymphoid tumors. A role for ATM in the development of sporadic T-cell chronic leukemias is supported by the finding of loss of heterozygosity at 11q22-23 and ATM mutations in leukemias carrying TCL-1 rearrangements. Approximately 14% of B-cell chronic lymphocytic leukemia (B-CLL), the most common adult leukemia, carry deletions of the long arm of chromosome 11 at 11q22-23. Loss of heterozygosity at 11q22-23 and, more recently, absence of ATM protein, have been associated with poor prognosis in B-CLL. To determine whether the ATM gene is altered in B-CLL, we have sequenced individual ATM exons in six B-CLL cases. We show that the ATM gene is mutated in a fraction of B-CLLs and that mutations can be present in the germ line of patients, suggesting that ATM heterozygotes may be predisposed to B-CLL.