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Blood, 2 July 2009, Vol. 114, No. 1, pp. 26-32.
Prepublished online as a Blood First Edition Paper on November 24, 2008; DOI 10.1182/blood-2008-09-176933.


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CLINICAL TRIALS AND OBSERVATIONS

The immunoglobulin gene repertoire of low-count chronic lymphocytic leukemia (CLL)–like monoclonal B lymphocytosis is different from CLL: diagnostic implications for clinical monitoring

Antonis Dagklis1,*, Claudia Fazi1,*, Cinzia Sala1, Valeria Cantarelli1, Cristina Scielzo1, Roberto Massacane2, Daniela Toniolo1, Federico Caligaris-Cappio1, Kostas Stamatopoulos3, and Paolo Ghia1

1 Laboratory and Unit of Lymphoid Malignancies, Department of Oncology, Università Vita-Salute San Raffaele e Istituto Scientifico San Raffaele, Milano, Italy; 2 Laboratorio Analisi ASL 22 - PO, Novi Ligure, Italy; and 3 Hematology Department and HCT Unit, G Papanicolaou Hospital, Thessaloniki, Greece

In the revised National Cancer Institute Working Group (NCI-WG)/International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for CLL, CLL-like monoclonal B lymphocytosis (MBL) is defined as the presence of less than 5 x 109/L B lymphocytes in the peripheral blood. However, the concentration of MBL in the blood is extremely variable. MBL in subjects with lymphocytosis require treatment at a rate of 1.1% per year and present immunoglobulin (IG) gene features and similar to good prognosis CLL. Little is known about low-count MBL cases, accidentally found in the general population. We analyzed IGHV-D-J rearrangements in 51 CLL-like MBL cases from healthy individuals, characterized by few clonal B cells. Seventy percent of the IGHV genes were mutated. The most frequent IGHV gene was IGHV4-59/61, rarely used in CLL, whereas the IGHV1–69 gene was lacking and the IGHV4-34 gene was infrequent. Only 2 of 51 (3.9%) MBL cases expressed a CLL-specific stereotyped HCDR3. Therefore, the IG gene repertoire in low-count MBL differs from both mutated and unmutated CLL, suggesting that the detection of MBL in an otherwise healthy subject is not always equivalent to a preleukemic state. Detailed IG analysis of individual MBL may help to identify cases that necessitate continuous clinical monitoring to anticipate disease progression.


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