General population low-count CLL-like MBL persist over time without clinical progression, though carrying the same cytogenetic abnormalities of CLL

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BlankGeneral population low-count CLL-like MBL persist over time without

clinical progression, though carrying the same cytogenetic abnormalities of CLL

1.. Fazi1,

2.. Lydia Scarfò2,

3.. Lorenza Pecciarini3,

4.. Francesca Cottini4,

5.. Antonis Dagklis1,

6.. Agnieszka Janus1,

7.. Talarico3,

8.. Cristina Scielzo5,

9.. Cinzia Sala6,

10.. a Toniolo6,

11.. Federico Caligaris-Cappio7,*, and

12.. Paolo Ghia1

+ Author Affiliations

1.. 1 Laboratory of B cell Neoplasia, Division of Molecular Oncology, Istituto

Scientifico San Raffaele, Milano, Italy;

2.. 2 Lymphoma Unit, Department of Onco-Hematology, Istituto Scientifico San

Raffaele, Milano, Italy;

3.. 3 Pathology Unit, Istituto Scientifico San Raffaele, Milano, Italy;

4.. 4 Universita Vita-Salute San Raffaele and Istituto Scientifico San

Raffaele, Milano, Italy;

5.. 5 Laboratory of Lymphoid Malignancies, Division of Molecular Oncology,

Istituto Scientifico San Raffaele, Milano, Italy;

6.. 6 Unit of Genetics of common disorder, Division of Genetics and Cell

Biology, Istituto Scientifico San Raffaele, Milano, Italy;

7.. 7 MAGIC (Microenvironment and Genes in Cancers of the blood)

Interdivisional Research Program, Istituto Scientifico San Raffaele, Milano,

Italy

1.. ?* Corresponding author; email: caligaris.federico@...

Abstract

Monoclonal B-cell Lymphocytosis (MBL) are classified as Chronic Lymphocytic

Leukemia (CLL)-like, atypical-CLL and CD5-negative (CD5-) MBL. The number of B

cells/µl divides CLL-like MBL into MBL associated with lymphocytosis (usually

detected in a clinical setting) and low-count MBL detected in the general

population (usually identified during population screening). After a median

follow-up of 34 months we re-evaluated 76 low-count MBL using 5-colour flow

cytometry: 90% of CLL-like MBL but only 44.4% atypical-CLL and 66.7% CD5- MBL

persisted over time. Population-screening CLL-like MBL had no relevant cell

count change and none developed an overt leukemia. In 50% of the cases FISH

revealed CLL-related chromosomal abnormalities including mono- or bi-allelic 13q

deletions (43.8%), trisomy 12 (1 case) and 17p deletions (2 cases). The analysis

of the T-cell receptor beta (TRBV) chains repertoire showed the presence of

monoclonal T-cell clones, especially among CD4highCD8low, CD8highCD4low T cells.

TRBV2 and TRBV8 were the most frequently expressed genes. This study indicates

that i) the risk of progression into CLL for low-count population-screening

CLL-like MBL is exceedingly rare and definitely lower than that of clinical MBL

and ii) chromosomal abnormalities occur very early in the natural history and

are possibly associated with the appearance of the typical phenotype.