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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4807-4812.
Prepublished online as a Blood First Edition Paper on March 3, 2005; DOI 10.1182/blood-2004-11-4394.


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NEOPLASIA

Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status

Pawel Grabowski, Magnus Hultdin, Karin Karlsson, Gerard Tobin, Anna Åleskog, Ulf Thunberg, Anna Laurell, Christer Sundström, Richard Rosenquist, and Göran Roos

From the Department of Medical Biosciences, Pathology, Umeå University, Umeå; Department of Medicine, Linköping University, Linköping; and Departments of Genetics and Pathology, Medical Sciences and Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden.

B-cell chronic lymphocytic leukemia (CLL) consists of 2 prognostic entities where cases with mutated immunoglobulin VH genes have better outcome than unmutated cases. VH-mutated CLLs display longer telomeres compared with unmutated cases and telomere length has been indicated to predict outcome, although the prognostic value of telomere length has not been fully established in CLL. We analyzed telomere length, VH gene mutation status, and clinical parameters in a large series of CLL. Telomere length was assessed by quantitative polymerase chain reaction (PCR), giving a very good correlation to telomere length estimated by Southern blotting (P < .001). The prognostic information given by mutation status (n = 282) and telomere length (n = 246) was significant (P < .001, respectively). Telomere length was a prognostic factor for stage A (P = .021) and stage B/C (P = .018) patients, whereas mutation status predicted outcome only in stage A patients (P < .001). Furthermore, mutated CLLs were subdivided by telomere length into 2 groups with different prognoses (P = .003), a subdivision not seen for unmutated cases (P = .232). Interestingly, the VH-mutated group with short telomeres had an overall survival close to that of the unmutated cases. Thus, by combining VH mutation status and telomere length, an improved subclassification of CLL was achieved identifying previously unrecognized patient groups with different outcomes. (Blood. 2005;105:4807-4812)


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