Quantification of newly produced B and T lymphocytes in untreated chronic lymphocytic leukemia patients.
BACKGROUND
The immune defects occurring in chronic lymphocytic leukemia are responsible for the frequent occurrence of infections and autoimmune phenomena, and may be involved in the initiation and maintenance of the malignant clone. Here, we evaluated the quantitative defects of newly produced B and T lymphocytes.


METHODS
The output of B and T lymphocytes from the production and maturation sites was analyzed in chronic lymphocytic leukemia patients and healthy controls by quantifying kappa-deleting recombination excision circles (KRECs) and T-cell receptor excision circles (TRECs) by a Real-Time PCR assay that simultaneously detects both targets. T-lymphocyte subsets were analyzed by six-color flow cytometric analysis. Data comparison was performed by two-sided Mann-Whitney test.


RESULTS
KRECs level was reduced in untreated chronic lymphocytic leukemia patients studied at the very early stage of the disease, whereas the release of TRECs+ cells was preserved. Furthermore, the observed increase of CD4+ lymphocytes could be ascribed to the accumulation of CD4+ cells with effector memory phenotype.


CONCLUSIONS
The decreased number of newly produced B lymphocytes in these patients is likely related to a homeostatic mechanism by which the immune system balances the abnormal B-cell expansion. This feature may precede the profound defect of humoral immunity characterizing the later stages of the disease.
Department of Hematology, Spedali Civili, Piazzale Spedali Civili 1, 25123, Brescia, Italy.
Marina
M
Motta
Marco
M
Chiarini
Claudia
C
Ghidini
Cinzia
C
Zanotti
Cinzia
C
Lamorgese
Luigi
L
Caimi
Giuseppe
G
Rossi
Luisa
L
Imberti
D000368:Aged; D001402:B-Lymphocytes / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000473:pathology*