Submitted September 8, 2008
Accepted November 9, 2008
The immunoglobulin gene repertoire of low-count CLL-like MBL is different from CLL: diagnostic implications for clinical monitoring
Antonis Dagklis, Claudia Fazi, Cinzia Sala, Valeria Cantarelli, Cristina Scielzo, Roberto Massacane, Daniela Toniolo, Federico Caligaris-Cappio*, Kostas Stamatopoulos, and Paolo Ghia
Laboratory and Unit of Lymphoid Malignancies, Department of Oncology, Universita Vita-Salute San Raffaele e Istituto Scientifico San Raffaele, Milano, Italy
Laboratorio Analisi A.S.L. 22 - P.O., Novi Ligure, Italy
Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece
* Corresponding author; email: caligaris.federico{at}hsr.it.
In the revised NCI-WG/IWCLL guidelines for CLL, CLL-like Monoclonal-B-Lymphocytosis (MBL) is defined as the presence of <5x109/L B lymphocytes 12 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 cytogenetic abnormalities similar to good prognosis CLL. Very 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 from a rural population of healthy individuals, characterized by few clonal B cells. Seventy % of the IGHV genes were mutated, with a predominance of IGHV3 genes. The most frequent IGHV gene was IGHV4-59/61, rarely used in CLL, while the IGHV1-69 gene was lacking and the IGHV4-34 gene was infrequent. Only 2/51 (3.9%) MBL cases expressed a CLL-specific stereotyped HCDR3. These results show that 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 pre-leukemic state. Detailed IG analysis of individual MBL may help to identify cases that necessitate continuous clinical monitoring to anticipate disease progression.
