Chronic Lymphocytic Leukemia

Kanti, R.; Sawitsky, Arthur; Jagathambal, Kandhasamy; Gartenhaus, W; Phillips, Elizabeth A.

doi:10.1016/s0025-7125(16)31123-3

Cited by 33 publications

(16 citation statements)

References 59 publications

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“…Patients can have stable disease, in terms of leukemic cell load and clinical symptoms, for a decade or longer (8). Several molecular correlates of poor clinical outcome have emerged in recent years.…”

Section: Introductionmentioning

confidence: 99%

In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells

et al. 2005

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Due to its relatively slow clinical progression, B cell chronic lymphocytic leukemia (B-CLL) is classically described as a disease of accumulation rather than proliferation. However, evidence for various forms of clonal evolution suggests that B-CLL clones may be more dynamic than previously assumed. We used a nonradioactive, stable isotopic labeling method to measure B-CLL cell kinetics in vivo. Nineteen patients drank an aliquot of deuterated water ( 2 H 2 O) daily for 84 days, and 2 H incorporation into the deoxyribose moiety of DNA of newly divided B-CLL cells was measured by gas chromatography/mass spectrometry, during and after the labeling period. Birth rates were calculated from the kinetic profiles. Death rates were defined as the difference between calculated birth and growth rates. These analyses demonstrated that the leukemic cells of each patient had definable and often substantial birth rates, varying from 0.1% to greater than 1.0% of the entire clone per day. Those patients with birth rates greater than 0.35% per day were much more likely to exhibit active or to develop progressive disease than those with lower birth rates Thus, B-CLL is not a static disease that results simply from accumulation of long-lived lymphocytes. Rather, it is a dynamic process composed also of cells that proliferate and die, often at appreciable levels. The extent to which this turnover occurs has not been previously appreciated. A correlation between birth rates and disease activity and progression appears to exist, which may help identify patients at risk for worsening disease in advance of clinical deterioration.

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Section: Introductionmentioning

confidence: 99%

In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells

et al. 2005

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“…1 The leukemia cells primarily are arrested in the G 0 /G 1 phase of the cell cycle and are resistant to programmed cell death. [2][3][4] Despite their apparent longevity in vivo, CLL cells often undergo spontaneous apoptosis under conditions that support the growth of human B-cell lines in vitro. 2,5 This implies that such ex vivo conditions lack essential survival factors and that the resistance to apoptosis is not intrinsic to the CLL cell.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4] Despite their apparent longevity in vivo, CLL cells often undergo spontaneous apoptosis under conditions that support the growth of human B-cell lines in vitro. 2,5 This implies that such ex vivo conditions lack essential survival factors and that the resistance to apoptosis is not intrinsic to the CLL cell. [5][6][7][8] Recently we found that a subset of blood mononuclear cells from patients with CLL could differentiate in vitro into large, round, adherent cells that attracted leukemia cells and protected them from undergoing apoptosis in vitro.…”

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confidence: 99%

Distinctive features of “nurselike” cells that differentiate in the context of chronic lymphocytic leukemia

Tsukada

Burger

Zvaifler

et al. 2002

Blood

230

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IntroductionB-cell chronic lymphocytic leukemia (CLL) is characterized by the steady accumulation of long-lived, monoclonal B cells in the blood, secondary lymphoid tissues, and marrow. 1 The leukemia cells primarily are arrested in the G 0 /G 1 phase of the cell cycle and are resistant to programmed cell death. [2][3][4] Despite their apparent longevity in vivo, CLL cells often undergo spontaneous apoptosis under conditions that support the growth of human B-cell lines in vitro. 2,5 This implies that such ex vivo conditions lack essential survival factors and that the resistance to apoptosis is not intrinsic to the CLL cell. [5][6][7][8] Recently we found that a subset of blood mononuclear cells from patients with CLL could differentiate in vitro into large, round, adherent cells that attracted leukemia cells and protected them from undergoing apoptosis in vitro. 9 Moreover, when CLL cells were removed from such adherent cells, the CLL cells experienced a rapid decline in viability unless replated onto the adherent cells.The effect of these adherent cells on CLL B-cell viability was mediated in part by the chemokine stromal-derived factor 1 (SDF-1), as demonstrated by the ability of synthetic SDF-1 to protect CLL cells from apoptosis after their removal from the adherent cells. 9 Moreover, this influence over CLL cell viability required cell-cell contact and could not be mimicked by coculture in conditioned media. Because these cells attracted CLL cells and supported their survival through a contact-dependent mechanism, we called them "nurselike" cells, or NLCs.Our prior studies found that NLCs expressed vimentin and SDF-1, but lacked expression of surface antigens found on T cells, B cells, or mature dendritic cells. Moreover, NLCs did not share cytogenetic alterations associated with the leukemia cell clone, indicating that they were derived from a distinct cell lineage. In this study, we performed immune phenotypic analyses of NLCs and examined whether blood cells from healthy donors could differentiate into NLCs that could sustain CLL cell viability in vitro. Materials and methods Cell preparationAfter obtaining informed consent, blood samples were collected from patients at the University of California San Diego (UCSD) Medical Center with diagnostic and immunophenotypic criteria for B-cell CLL. The patients were not treated previously and had not received recombinant growth factors or exogenous cytokines. Blood mononuclear cells were isolated by density-gradient centrifugation over Ficoll-Hypaque (Pharmacia, Uppsala, Sweden). The mononuclear cells were used fresh or suspended in fetal calf serum (FCS) containing 5% dimethyl sulfoxide (DMSO) for storage in liquid nitrogen. The viability of the CLL cells was always more than 85% at the initiation of the cell culture, as determined by their ability to exclude propidium iodide (PI). For this the cells were suspended in 5 g/mL PI (Molecular Probes, Eugene, OR) for 15 minutes at 37°C and then evaluated via flow cytometry. All CLL cell samples examined contained ...

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“…B cell chronic lymphocytic leukemia (B-CLL), a monoclonal expansion of mature CD5-expressing B lymphocytes, is a heterogeneous disease that affects primarily individuals over 50 years of age (1). Even though B-CLL is the most common leukemia in the Western hemisphere (2), the events that select out an individual normal B cell clone and usher it toward leukemic transformation remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Remarkably similar antigen receptors among a subset of patients with chronic lymphocytic leukemia

Ghiotto¹,

Fais²,

Valetto³

et al. 2004

J. Clin. Invest.

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192

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approved these studies. From a cohort of 237 patients with clinical and laboratory features of B-CLL, 25 patients with expansions of CD5 + /CD19 + B cells expressing surface membrane IgG or IgA were chosen and analyzed. All of the patients with surface membrane IgM + cells were obtained randomly; some of the IgG + cases were provided by others because of their surface membrane phenotype and therefore were not randomly acquired. Some patients and the V gene Nonstandard abbreviations used: arsonate (Ars); B cell antigen receptor (BCR); B cell chronic lymphocytic leukemia (B-CLL); double-stranded DNA (dsDNA); framework region (FR); germinal center (GC); heavy chain third complementarity-determining region (HCDR3); light chain third complementarity-determining region (LCDR3); single-stranded DNA (ssDNA); web antibody modeling (WAM).

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Chronic Lymphocytic Leukemia

Cited by 33 publications

References 59 publications

In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells

In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells

Distinctive features of “nurselike” cells that differentiate in the context of chronic lymphocytic leukemia

Remarkably similar antigen receptors among a subset of patients with chronic lymphocytic leukemia

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