'Remarkable' Difference in CLL Cells Derived from Different Tissue

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[2817] Remarkable Differences in Cellular Activation State and

Migratory and Proliferative Potential among Clonal Cells Derived from

Different Tissues of Chronic Lymphocytic Leukemia Patients. Session

Type: Poster Session, Board #46-III

Rajendra N. Damle, Taraneh Banapour, Sonal Temburni, Tarun Wasil,

E. Kolitz, L. , Barbara Sherry, Kanti R. Rai,

Chiorazzi Laboratory of Experimental Immunology, Feinstein

Institute for Medical Research; NS-LIJ Health System, Manhasset, NY,

USA; Don Monti Division of Hematology and Oncology, North Shore

University Hospital; NS-LIJ Health System, Manhasset, NY, USA;

Laboratory of Cytokine Biology, Feinstein Institute for Medical

Research; NS-LIJ Health System, Manhasset, NY, USA; Hematology and

Oncology Unit, Long Island Jewish Medical Center, New Hyde Park, NY,

USA

An antigen-independent process that takes place in the bone marrow

(BM) leads to the birth of B cells from bone marrow precursors. Cross-

talk between components of the microenvironment of BM or secondary

lymphoid compartment(s), eg. spleen (SP), nurtures the subsequent

evolution of B cells and governs in large part the natural history of

normal B cells and B cell malignancies including chronic lymphocytic

leukemia (B-CLL).

Interaction of B cells with stromal elements confers upon them

features enabling their transient sequestration, proliferation and

extended survival. In this report we have compared the

characteristics of clonal B-CLL cells obtained from paired specimens

(peripheral blood, PB with corresponding BM or SP obtained within an

interval of less than 1 month of each other) from 17 individual

untreated B-CLL patients. These cells were tested by surface

immunofluorescence and flow cytometry for their expression of a panel

of chemokine receptors (CCR -1, -2, -4, and -7 and CXCR-1, -2, -3,

and -4) and markers of cellular activation (CD23, CD62L, CD69, CD71

and HLA-DR).

The relative age of the B cells (telomere length) and their ability

to maintain telomere length (telomerase activity) were studied in

paired BM/SP and PB samples from 15 of these cases. Although PB-, BM-

and SP-derived B cells expressed activation markers, specifically,

the percentages of cells expressing ZAP-70 and Ki-67 were

significantly higher in BM- and SP-derived B cells than those

expressed by corresponding PB-derived B cells (p<0.01).

Increase in extent of CD38-positivity among members of the clone

correlates with poor prognosis in B-CLL. Interestingly, in cases with

low CD38 expression (<30% cells expressing CD38), the percentage of B-

CLL cells expressing CXCR3 and CCR7 was significantly higher among PB-

B cells, than BM/SP-derived B cells. No such differences existed in

cases with high CD38 expression. This suggests a role for these

receptors and their ligands in maintaining homeostasis of B-CLL cells

in this subset of cases (that does not show remarkable progression of

disease). In each of the 15 cases studied BM and SP-B cells had

significantly higher telomerase activity (p<0.01) than those in PB,

although telomere lengths of B cells from both sources were

comparable. These findings highlight important differences in

cellular kinetics among lymphoid compartments in B-CLL.