Determination of the plasma cell labelling index with bromodeoxyuridine in a double fluorescence technique

Lokhorst, Henk M.; Boom, Saskia E.; Bast, Bert J.E.G.; Ballieux, R. E.

doi:10.1111/j.1365-2141.1986.tb04119.x

Cited by 36 publications

(11 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[3][4][5][6][7] "Traditional" methods for assessing proliferation in myeloma, i.e. 3 H-thymidine uptake, 3,8 bromodeoxyuridine uptake, [9][10][11] flow-cytometric cell-cycle analysis using propidium iodide 6 or assessment of Ki-67 expression, 12 did not find widespread use. This is mainly due to the not negligible effort involved in these methods, and the assumption that similar groups of patients could be identified either by conventional prognostic factors, e.g.…”

Section: Introductionmentioning

confidence: 99%

Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma

Hose

Rème²,

Hielscher³

et al. 2010

Haematologica

195

196

View full text Add to dashboard Cite

BackgroundProliferation of malignant plasma cells is a strong adverse prognostic factor in multiple myeloma and simultaneously targetable by available (e.g. tubulin polymerase inhibitors) and upcoming (e.g. aurora kinase inhibitors) compounds. Design and MethodsWe assessed proliferation using gene expression-based indices in 757 samples including independent cohorts of 298 and 345 samples of CD138-purified myeloma cells from previously untreated patients undergoing high-dose chemotherapy, together with clinical prognostic factors, chromosomal aberrations, and gene expression-based high-risk scores. ResultsIn the two cohorts, 43.3% and 39.4% of the myeloma cell samples showed a proliferation index above the median plus three standard deviations of normal bone marrow plasma cells. Malignant plasma cells of patients in advanced stages or those harboring disease progressionassociated gain of 1q21 or deletion of 13q14.3 showed significantly higher proliferation indices; patients with gain of chromosome 9, 15 or 19 (hyperdiploid samples) had significantly lower proliferation indices. Proliferation correlated with the presence of chromosomal aberrations in metaphase cytogenetics. It was significantly predictive for event-free and overall survival in both cohorts, allowed highly predictive risk stratification (e.g. event-free survival 12.7 versus 26.2 versus 40.6 months, P<0.001) of patients, and was largely independent of clinical prognostic factors, e.g. serum β2-microglobulin, International Staging System stage, associated high-risk chromosomal aberrations, e.g. translocation t(4;14), and gene expression-based high-risk scores. ConclusionsProliferation assessed by gene expression profiling, being independent of serum-β2-microglobulin, International Staging System stage, t(4;14), and gene expression-based risk scores, is a central prognostic factor in multiple myeloma. Surrogating a biological targetable variable, gene expression-based assessment of proliferation allows selection of patients for riskadapted anti-proliferative treatment on the background of conventional and gene expressionbased risk factors.

show abstract

Section: Introductionmentioning

confidence: 99%

Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma

Hose

Rème²,

Hielscher³

et al. 2010

Haematologica

195

196

View full text Add to dashboard Cite

show abstract

“…The PCLI is a slide-based immunofluorescence technique that uses antibodies against BrdU, which are incorporated into actively dividing plasma cells, thereby providing the percentage of plasma cells in the S-phase of the cell cycle. [6][7][8] Multiple authors have confirmed the independent prognostic value of an elevated PCLI of Ͼ 1%, which is predictive of shorter time to progression 9 and decreased survival. [10][11][12] To test our hypothesis, we studied 176 patients seen at Mayo Clinic between 1985 and 2005 with newly diagnosed myeloma who had a measurable PCLI of Ն 0.5%, which was obtained at time of diagnosis and again 4 months after initiation of therapy.…”

Section: Methodsmentioning

confidence: 99%

Reduction in plasma cell proliferation after initial therapy in newly diagnosed multiple myeloma measures treatment response and predicts improved survival

Larsen

Chee

Lust

et al. 2011

Blood

View full text Add to dashboard Cite

Standard myeloma treatment response criteria are determined principally by changes in the monoclonal protein. Reduction in the size of the proliferative component of malignant plasma cells may be an additional metric of assessing response to therapy. We retrospectively analyzed 176 patients with newly diagnosed myeloma with a measurable plasma cell labeling index (PCLI) at diagnosis and repeat measurement 4 months after initiation of therapy. PCLI response was defined as a > 60% reduction. Baseline PCLI is an independent prognostic factor; therefore, we categorized patients into 3 groups: PCLI > 3% (high), > 1% (intermediate), and < 1% (low). Patients achieving a greater PCLI response had improved median overall survival of 54 months compared with 29 months in nonresponders (P ‫؍‬ .02). Improved median overall survival with PCLI response occurred in the high initial PCLI group (28 vs 7 months; P ‫؍‬ .003) and intermediate group (64 vs 24 months; P ‫؍‬ .002). The application of PCLI response and serum M-spike response together provided further prognostic information. On multivariate analysis, the prognostic value of PCLI response was independent of ␤ 2 -microglobulin, elevated creatinine, serum M-spike response, and baseline PCLI. We conclude that a significant reduction in plasma cell proliferation in patients with newly diagnosed myeloma is an important predictor of survival. (Blood. 2011; 118(10):2702-2707)

show abstract

“…

Mellstedt et al, 1984;Lokhorst et al, 1985). These findings suggested that the malignant transformation leading to the development of MM already occurred in a precursor of the plasma cell.

…”

mentioning

confidence: 84%

“…Neoplastic cells of transplanted murine plasmacytomas have been demonstrated to differentiate from small non-secreting clonogenic cells to large plasmacytoid cells secreting the homogenous Ig (Rohrer et al, 1977;Daley, 1981). In man, precursor cells expressing the myeloma idiotype in various stage of differentiation were demonstrated in the peripheral blood and in the BM (reviewed in Mellstedt et al, 1982;Mellstedt et al, 1984;Lokhorst et al, 1985). These findings suggested that the malignant transformation leading to the development of MM already occurred in a precursor of the plasma cell.…”

mentioning

confidence: 99%

The 5T2 mouse multiple myeloma model: characterization of 5T2 cells within the bone marrow

Croese

Nunes²,

Rádl³

et al. 1987

Br J Cancer

View full text Add to dashboard Cite

Mellstedt et al., 1984;Lokhorst et al., 1985). These findings suggested that the malignant transformation leading to the development of MM already occurred in a precursor of the plasma cell. Further support for this hypothesis was offered by the observation of chromosomal abnormalities in plasma cells as well as in cells with a B-lymphocyte phenotype of a patient with plasma cell leukaemia (MacKenzie et al., 1985). These chromosomal abnormalities showed a similarity with those reported in cases of MM. However, functional proof of the participation of idiotype-bearing B-cells in the myeloma clone has not yet been achieved. In vitro stimulation of idiotype-bearing B-cells in the presence of mitogens such as pokeweed mitogen or Staphylococcus aureus did not lead to a subsequent differentiation of these cells into a more mature Ig-secreting phenotype (Peest et al., 1984;Bloem, 1985). Moreover, it had been suggested by other investigators that the idiotype-bearing lymphocytes in MM were in fact T-lymphocytes binding the myeloma-Ig by Fc-receptors with specificity for its isotype (Hoover et al., 1981). Recently, myeloma precursors of lymphoid morphology that lacked surface and cytoplasmic Ig, but expressed the acute lymphoblastic leukaemia antigen (CALLA) were identified in the BM of patients with MM. In vitro stimulation of these cells with the phorbol ester 12-0-tetradecanoyl-phorbol-13 acetate (TPA) resulted in their transformation into plasma cells that synthesized the myeloma-specific Ig (Caligaris-Cappio et al., 1985). This observation indicated the existence of a functional relationship between more differentiated MM-cells and their precursors. However, the exact role of the idiotypebearing B-lymphocyte has not become clear in that study. A suitable experimental animal model for MM is a prerequisite for detailed studies on the basic biological mechanisms of this neoplasm. Recently, spontaneous multiple myeloma developing in a number of aging C57BL/KaLwRij mice has been observed (Radl et al., 1985a). This mouse MM resembles the human disease in several respects. In contrast with the induced mouse plasmacytomas, it is of spontaneous origin and the MM cells are predominantly located in the BM; a circulating monoclonal myeloma protein reflects the extent of the tumour load, and, in many cases, the MM is complicated by severe osteolytic bone destruction (Radl et al., 1985a). Among the different established transplantable ST MM lines, the 5T2 MM has been studied most extensively (Radl et al., 1985b MiceMale and female C57BL/KaLwRij mice from the colony of the TNO Institute for Experimental Gerontology were used in all experiments. They were maintained under conventional conditions. Detailed information on husbandry, health status, survival data, and age-associated pathology of this strain has been published elsewhere (Van Zwieten et al.,

show abstract

Determination of the plasma cell labelling index with bromodeoxyuridine in a double fluorescence technique

Cited by 36 publications

References 5 publications

Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma

Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma

Reduction in plasma cell proliferation after initial therapy in newly diagnosed multiple myeloma measures treatment response and predicts improved survival

The 5T2 mouse multiple myeloma model: characterization of 5T2 cells within the bone marrow

Contact Info

Product

Resources

About