2321 Leukemia & Lymphoma, November 2012; 53(11): 2321–2325 © 2012 Informa UK, Ltd. ISSN: 1042-8194 print / 1029-2403 online DOI: 10.3109/10428194.2012.698277 Correspondence: Arnon P. Kater, MD, PhD, Internist-Hematologist, Dept. of Hematology, Academic Medical Center Amsterdam, University of Amsterdam, he Netherlands. Tel: + 31-20-5665785. E-mail: a.p.kater@amc.nl Received 14 May 2012; accepted 19 May 2012 CLL YOUNG INVESTIGATORS’ MEETING 2011 Chronic lymphocytic leukemia specific T-cell subset alterations are clone-size dependent and not present in monoclonal B lymphocytosis G. Doreen te Raa 1,2 , Sanne H. Tonino 1 , Ester B. M. Remmerswaal 2,3 , Arend Jan van Houte 4 , Harry R. Koene 5 , Marinus H. van Oers 1 & Arnon P. Kater 1 1 Department of Hematology, 2 Laboratory of Experimental Immunology and 3 Renal Transplant Unit, Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands and 4 Department of Medical Microbiology and Immunology, and 5 Department of Internal Medicine, St Antonius Hospital, Nieuwegein, The Netherlands Introduction By use of sensitive low cytometry, it was recently discovered that small populations of monoclonal B-lymphocytes with a typical chronic lymphocytic leukemia (CLL) immunopheno- type (termed monoclonal B lymphocytosis, or MBL) can be found in the peripheral blood of healthy adults above the age of 40 with an estimated prevalence of 3–12% [1–3]. Individu- als with MBL are usually discovered accidentally, either in cases of asymptomatic lymphocytosis (clinical MBL; cMBL) or by population screening for research purposes (low count MBL; lcMBL). Patients with cMBL have an average risk of developing CLL requiring treatment of 1–2% per year [2–5], whereas most patients with lcMBL do not progress over time [6]. Although MBL and CLL are biologically closely related [7], currently there is an arbitrarily chosen cut-of value of CD19 of 5.0  10 9 /L; cases with a CLL clone with CD19  5.0  10 9 /L are deined as CLL, and cases with a CLL clone with CD19  5.0  10 9 /L are deined as MBL [8]. Several studies have described an expansion of both CD4 + [9,10] and CD8 + cells [10–12] in CLL, which showed an antigen experienced (memory and efector), activated phenotype [10–13]. Furthermore, clonal and oligoclonal expansions were found within both CD4 + and CD8 + T-cell compartments with a restricted T-cell receptor (TCR) rep- ertoire [14,15]. In addition, there is evidence for decreased T-cell function in CLL based on impaired immunological synapse formation [16,17]. Whether T-cell disturbances already exist in patients with cMBL has been poorly investigated to date. Recently, it has been shown that expansion of T cells exists in patients with CLL Rai stage 0 with a rather small CLL clone (WBC  28.0  10 9 /L) [18]. Although there is evidence for a skewed TCR repertoire in MBL [6,19], there are no data on absolute T cell numbers in MBL. We investigated whether the expansion of T-cell subsets exists in cMBL to obtain more insight into the consequences of CLL tumor burden on T-cell alterations and to investigate whether T-cell numbers follow the deined cut-of for MBL and CLL. Design and methods Patients Peripheral blood mononuclear cells (PBMCs) from previously untreated patients with cMBL and age-matched patients with CLL were collected at diagnosis or during routine follow-up visits at the Department of Hematology of the Saint Antonius Abstract In patients with chronic lymphocytic leukemia (CLL), efector and memory CD4  and CD8  T cells are expanded. We investigated whether these CLL speciic T-cell expansions also occur in monoclonal B lymphocytosis (MBL), the pre-leukemic state of CLL, which is currently distinguished from CLL by an arbitrarily chosen cut-of value of CD19 of 5.0  10 9 /L. Whereas an increase in efector and memory CD4  and CD8  T cells was found in CLL, these expansions could not be found in MBL. Although a signiicant correlation was found between absolute B cell count (CD19) and T cell numbers, correlation coeicients were rather low. Therefore, we analyzed whether an optimal threshold for CD19 number could be deined which best related to an expansion of T cells. The B-cell threshold that best predicted expansion of CD3 , CD4  and CD8  T cells, respectively, was 10  10 9 /L. Our study indicates that a higher cut-of value than the current 5.0  10 9 /L relates better to the biological impact of CLL. Keywords: MBL, CLL, T cell Leuk Lymphoma Downloaded from informahealthcare.com by University Library SZ 100 on 11/15/12 For personal use only.