SEARCH · PubMed Health

Results for “CLL”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources

PubMed1997

B-CLL cells with unusual properties.

In studies concerning the interaction of B-CLL cells and Epstein-Barr virus (EBV), we encountered one patient whose cells had several unusual properties. In addition to the B-cell markers, the CLL cells expressed the exclusive T-cell markers CD3 and CD8 and carried a translocation t(18,22)(q21;q11), involving the bcl-2 and Ig lambda loci. The patient represents the 4th reported CLL case with this translocation. The CLL cells could be infected and immortalized by the indigenous and by the prototype B958 virus in vitro. The T-cell markers were not detectable on the established lines. In all experiments the immortalized lines originated from the CLL cells. Their preferential emergence over virus-infected normal B cells may be coupled to the high expression of the bcl-2 gene due to the translocation. In spite of the sensitivity of CLL cells to EBV infection in vitro, no EBNA-positive cells were detected in the ex vivo population. In vitro, we could generate cytotoxic function in T-lymphocyte cultures which acted on autologous EBV-infected CLL cells. Therefore we assume that if such cells emerged in vivo they were eliminated by the T-cell response.

Aged↗

PubMed1986

Abnormal T cell function in early-stage chronic lymphocytic leukemia (CLL) patients.

Significant alterations in T cell subpopulations and function occur in chronic lymphocytic leukemia (CLL) patients. We studied whether abnormalities in peripheral blood T cell parameters were present in 15 untreated early stage CLL patients (ie, Rai stage 0, 1, 2). Seven of the nine patients showed decreased T helper support as compared to control T cells for pokeweed mitogen (PWM)-induced control B cell proliferation (ie, patient 6,063 +/- 1,434 cpm vs control 14,894 +/- 121 cpm). All stage 0 and 1 patients showed a marked impairment of T helper activity for control B cell proliferation (patient T = 7,752 +/- 1,137 cpm vs control T = 14,894 +/- 121 cpm). In a separate assay system, six of nine CLL patients showed T suppressor activity for control B cell proliferation greater than control T cell suppressor activity. Four patients were stage 0 and 1. CLL patients demonstrated markedly impaired T cell support for control B cell immunoglobulin synthesis compared to control T cells (188 +/- 28 vs 869 +/- 56 hemolytic plaque-forming cells (HePFC)/culture, respectively). Control T cells showed increasing support for control B cell immunoglobulin synthesis with increasing T:B cell ratios (869 +/- 56 vs 1,265 +/- 48 HePFC/culture, at 1:1 and 2:1 T:B cell ratios, respectively). In contrast, five of eight CLL patients' T cells showed no improvement in control B cell immunoglobulin synthesis with increasing T:B cell ratios (795 +/- 56 vs 569 +/- 48 HePFC/culture, at 1:1 and 2:1 T:B cell ratios, respectively). There was no direct correlation with CLL T cell-mediated suppression of B cell proliferation and suppression of B cell immunoglobulin synthesis. These studies suggest there is a complex array of abnormal immunoregulatory T cell function in early stage CLL. These include a prominent T helper dysfunction and more variable excessive suppressor activity. The relationship of these findings to the basic disease process remains to be elucidated.

Antibody-Producing Cells↗

PubMed2006

Use of a blocking antibody method for the flow cytometric measurement of ZAP-70 in B-CLL.

BACKGROUND: In this study we developed a method to measure the amount of ZAP-70 [zeta accessory protein] in B-CLL cells without relying on the ZAP-70 expression of patient B or T cells to normalize fluorescence intensity. METHODS: B-CLL cells were fixed with formaldehyde before surface staining with gating antibodies CD19PC5 and CD5FITC. The cells were permeabilized with saponin, and the ZAP-70 antigen was blocked in one tube with unlabeled antibody to ZAP-70 [clone 1E7.2]. Zap-70-PE was then added to this tube. ZAP-70-PE was added to a second tube without unlabeled antibody to ZAP-70. The mean fluorescence intensity of the ZAP-70 in the tube without unlabeled antibody divided by the mean fluorescence intensity of the ZAP-70 in the tube with unlabeled antibody equals the RATIO of total fluorescence to non-specific ZAP-70 fluorescence in the B-CLL cells. In a second method of analysis, a region is created in the histogram showing ZAP-70 fluorescence intensity in the tube with unlabeled antibody to ZAP-70. This region is set to 0.9% positive cells. This same region is then used to measure the % positive [%POS] ZAP-70 cells in the tube without unlabeled antibody to ZAP-70. The brighter the ZAP-70 fluorescence above the non-specific background, the higher the %POS. RESULTS: Due to the varying amount of non-specific staining between patient B-CLL cells and other cells, the blocking antibody method yielded a more quantitative and reproducible measure of ZAP-70 in B-CLL cells than other methods, which use the ratio of B-CLL fluorescence to normal B or T-cell fluorescence. Using this improved method, ZAP-70 was determined to be negative if the RATIO was less than 2:1 and positive if the RATIO was greater than 2:1. ZAP-70 was determined to be negative if the %POS was less than 5% and positive if the %POS was greater than 5%, a cut-off value lower than previous values published, due to exclusion of non-specific staining. Both cut-offs were based upon patient specimen distribution profiling. CONCLUSIONS: Use of a blocking antibody resulted in a robust, reproducible clinical B-CLL assay that is not influenced by the need to measure the amount of ZAP-70 in other cells. ZAP-70 results segre gate patients into indolent and aggressive groups suggested by published clinical outcomes.

ADP-ribosyl Cyclase 1↗

PubMed2006

Bortezomib induces different apoptotic rates in B-CLL cells according to IgVH and BCL-6 mutations.

BACKGROUND: B-cell chronic lymphocytic leukemia (B-CLL) is a remarkably heterogeneous disorder. Some patients have an indolent disease whereas others undergo a more agressive presentation needing treatment. New therapeutics approaches are necessary for the treatment of B-CLL. Bortezomib (Btz), is a proteasome inhibitor, currently undergoing clinical trials whose function, at least in part, by stabilizing the IkappaBalpha protein and inhibiting NFkappaB activation. OBJECTIVE: The objective of this work was to study the effects of Btz on isolated human B-CLL cells, in vitro, and to correlate the differential rates of apoptosis induction with biological variables. MATERIAL AND METHODS: 31 B-CLL samples, from patients in stage A of Binet were used for this study, and the apoptotic effect of Btz on these cells was measured. RESULTS: Our data show that Btz treatment of B-CLL cells induces apoptosis in a time and dose-dependent manner. The apoptosis induction is mediated in part by inhibition of NFkappaB and is dependent on caspases activation. Interesting, in IgVH mutated cells, Btz have statistically significant differences in their in vitro activity on B-CLL cells according to their BCL-6 mutational status. CONCLUSIONS: Btz is a promising pharmacologic agent for the treatment of B-CLL, but its efficacy seems to be related to IgVH and BCL-6 mutational status, therefore, it could be interesting to further investigate the mechanisms involved in the different behavior of the cells in response to apoptosis induction by this drug.

ADP-ribosyl Cyclase 1↗

PubMed1991

The leukemic B-cell population of patients with monoclonal lymphocytosis of undetermined significance (MLUS) are functionally distinct from the chronic lymphocytic leukemia (CLL) derived cell population.

Some patients with CLL survive for decades with a stable lymphocytosis without other signs of progression of the disease. This condition has been termed monoclonal lymphocytosis of undetermined significance (MLUS). The aim of the present study was to search for functional differences between the monoclonal B-cell population of CLL (n = 3) and MLUS (n = 5) patients. MLUS derived B-cell populations were susceptible to Epstein-Barr virus (EBV) infection measured as the production of EB nuclear antigen (EBNA) whereas CLL derived cells were resistant. In 4 out of 5 MLUS patients, lymphoblastoid cell line (LCL) like cell-clumps were formed, but not in CLL. The clonal B-cell population from 2 of 5 MLUS patients was immortalized by EBV (LCL restricted to the expression of one Ig light chain) while no cell line emerged from the CLL patients. Phorbol esters induced cell to cell adhesion of MLUS and normal B cells but not of CLL derived cells. This study further enlarges previous observations and strengthens the assumption that MLUS clonal B cells are functionally close to normal B cells while CLL B cells display various functional abnormalities.

Antigens, Surface↗

PubMedDate not supplied

Serum levels of helper factors (IL-1 alpha, IL-1 beta and IL-6), T-cell products (sCD4 and sCD8), sIL-2R and beta 2-microglobulin in patients with B-CLL and benign B lymphocytosis.

Chronic B-lymphocytic leukemia (B-CLL) cells may be regulated by immune functions. In an attempt to analyze such functions, helper factors (IL-1 alpha, IL-1 beta and IL-6), T-cell products (sCD4 and sCD8) and sIL-2R and beta 2-microglobulin were measured in serum of patients at different stages of the disease. Patients were classified as having monoclonal lymphocytosis of undetermined significance (MLUS), stable or progressive B-CLL respectively. A significant, but modest, increase of IL-1 alpha was found in B-CLL as well as in MLUS patients whereas IL-6 levels were increased in MLUS only. sCD8 levels were increased both in MLUS and B-CLL but augmented sCD4 concentrations were found statistically significant only in progressive B-CLL. beta 2-microglobulin and sIL-2R were related to the extent of the monoclonal B-cell fraction. The data indicate an increased T-suppressor activity in both MLUS and B-CLL patients and a selective increase of helper T-cell activity in progressive B-CLL. A possible immunoregulatory influence of helper T cells on disease progression is discussed.

Adult↗

PubMed1995

Beta-tubulin and P-glycoprotein: major determinants of vincristine accumulation in B-CLL cells.

Vincristine (VCR) accumulation in chronic lymphatic leukemia of B-cell origin (B-CLL) has recently been shown not to be inversely correlated to P-glycoprotein (PGP) levels. Therefore, we studied, in addition to PGP expression and accumulation of VCR, the cellular beta-tubulin content in quiescent and rhIL-2 activated B-CLL cells. VCR mediates cytotoxicity by binding to tubulin. Constitutive beta-tubulin levels in B-CLL cells varied considerably. Upon activation with rhIL-2, beta-tubulin expression increased significantly. Therefore, tubulin levels could be correlated over a wide range to VCR accumulation. When the PGP-mediated drug efflux was blocked by verapamil (VRP), tubulin levels correlated linearly to VCR accumulation. All B-CLL cases expressed PGP at different levels. There was no linear correlation between PGP expression and VCR accumulation. A modulation factor m was defined as a quotient of VCR accumulation in the presence and absence of VRP to define the extent by which VRP inhibited a steady-state accumulation of VCR. The factor allowed discrimination between B-CLLs expressing low versus high PGP, irrespective of the levels of tubulin. However, PGP and beta-tubulin levels together were predictive for VCR accumulation in steady state. There was no uniform-accumulation defect for VCR in B-cell CLL because beta-tubulin and PGP were expressed independently. Non PGP-mediated VCR transport seems to play a minor role in B-cell CLL. Leukemia-associated varying of cytoskeletal organization in B-cell CLL might be one reason for the diverse cellular responses to receptor-mediated signals.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

The levels of TNF alpha, IL4 and IL10 production by T-cells in B-cell chronic lymphocytic leukaemia (B-CLL).

Tumour necrosis factor alpha (TNF alpha), interleukin (IL) 4 and IL10 are important for the growth and survival of the leukaemic cells in B-cell chronic lymphocytic leukaemia (B-CLL). The present study investigates the production of TNF alpha, IL4 and IL10 in patients with B-CLL. Significant increases in the TNF alpha and IL4 mean levels compared to normal control CD2(+)-cells were observed for B-CLL lymphocytes (TNF alpha: P=0.0004 and IL4: P=0.0026). By contrast, the mean level of IL10 produced by purified B-CLL CD2(+)-cells was significantly lower than that seen with normal control T-cells (P=0.0136). No significant difference in the percentage (%) of T-cells that expressed cytoplasmic TNF alpha, IL4 and IL10 was observed between B-CLL and normal T-cells. However, a significant increase in the mean level of intracellular TNF alpha and IL4 expression was observed in B-CLL compared with normal control T-cells (TNF alpha: P=0.031; IL4: P=0.0027). The increased expression of cytoplasmic TNF alpha and IL4 appeared to be associated with increased cytokine production in the tested samples. The differences observed with some B-CLL cases in the production of TNF alpha, IL4 and IL10 by peripheral blood T-cells may suggest survival mechanisms for the leukaemic cells in these patients.

CD4-CD8 Ratio↗

PubMed2001

UCN-01 induces cytotoxicity toward human CLL cells through a p53-independent mechanism.

OBJECTIVES: UCN-01, a novel protein kinase C inhibitor, is currently being tested in phase I clinical trials after being noted to induce apoptosis in lymphoid cell lines. We sought to study the in vitro activity of UCN-01 against human chronic lymphocytic leukemia (CLL) cells and potential mechanisms of action for inducing this cytotoxicity. METHODS: Detailed in vitro studies were performed from tumor cells derived from patients with CLL cells following attainment of written informed consent. RESULTS: The 50% loss of viability (LC(50)) in mononuclear cells from CLL patients (n = 10) following exposure to UCN-01 for 4 days was 0.4 microM (95% CI +/- 0.21; range 0.09-1.16). Loss of viability in human CLL cells correlated with early induction of apoptosis. Exposure of CLL cells to 0.4 and 5.0 microM of UCN-01 resulted in decreased expression of p53 protein. We therefore investigated the dependence of UCN-01 on intact p53 by exposing splenocytes from wild-type (p53(+/+)) and p53 null (p53(-/-)) mice, which demonstrated no preferential cytotoxicity when compared to the marked differential induced by F-Ara-A and radiation. CONCLUSIONS: UCN-01 has significant in vitro activity against human CLL cells that appears to occur independent of p53 status. While demonstration of in vitro cytotoxicity does not establish in vivo efficacy, the findings described support the early introduction of UCN-01 into clinical trials for patients with B-CLL.

Alkaloids↗

PubMed1993

Biology of the neoplastic lymphocyte in B-CLL.

Immunological markers have identified the proliferating lymphocyte in CLL as a mature B lymphocyte which, unlike lymphocytes in other B cell malignancies, expresses low amounts of surface membrane immunoglobulin (smIg), forms rosettes with mouse erythrocytes and expresses the CD5 marker. It has been postulated that Ly1 B cells (the murine counterpart of human CD5+B cells) constitute a separate B cell lineage. Whether the CD5 marker defines a discrete lineage or is a maturation marker is one of the main issues that might be solved in the near future. Another recent advance has been the discovery that the B lymphocyte in CLL is in an activated state and can be induced to differentiate. Using B cell mitogens and somatic hybridization, it has been demonstrated that the B-CLL lymphocyte is frequently involved in the production of natural autoantibodies and expresses a restricted set of genes. These results may provide a basis for passive immunotherapy using anti-idiotypic antibodies. Hypogammaglobulinaemia is a distinct feature of B-CLL, observed in 60% of patients. It may result from impaired function of residual normal B cells. This could occur as a consequence of progressive dilution of normal non-clonal B cells, or because normal B cells are downregulated by an unknown mechanism. This decrease in or inhibition of normal CD5-B cells could also explain the classical inability of patients with B-CLL to respond to new antigenic challenges, since Ly1 B cells have been claimed to be unable to respond to exogenous antigens. Although regulatory abnormalities in T cells may play a role in the induction of hypogammaglobulinaemia, data concerning helper, suppressive, NK and ADCC cells are contradictory and fail to establish firmly the contribution of these cells in the development of hypogammaglobulinaemia. Associated autoimmune phenomena are a prominent complication in CLL. They are related to the presence of autoantibodies directed mainly against blood components, which in most cases are not the product of the malignant clone. The relationship between autoimmune phenomena and hypogammaglobulinaemia is not definitively substantiated. That hypogammaglobulinaemia may determine the loss of some anti-idiotypic antibodies designed to antagonize autoimmune clones is an attractive hypothesis, which needs to be substantiated. Several recurrent chromosomal abnormalities, such as trisomy 12, structural aberrations of the 13q14 and 14q32 bands, are frequently observed in B-CLL. Less frequently, alterations of chromosomes 11, 6, 18, 3, 17, 7 and 8 have been reported.(ABSTRACT TRUNCATED AT 400 WORDS)

Agammaglobulinemia↗

PubMed2001

Increased serum levels of soluble Fas in progressive B-CLL.

Clinical progression of B-cell chronic lymphocytic leukemia (B-CLL) depends on survival and accumulation of leukemic cells, regulated in part by physical cell contact and soluble molecules. Here we have studied the Fas/FasL system in relation to clinical progression in B-CLL. Serum levels of soluble Fas (sFas) and FasL (sFasL) were determined by ELISA in 43 progressive and 40 non-progressive B-CLL patients and in 21 control individuals. Correlation between sFas serum levels and clinical progression, stage and survival were statistically analyzed. We found high levels of sFas in B-CLL sera correlated with disease progression (p<0.01). In addition, higher sFas levels were found in patients in stages II, III and IV in comparison to patients in stage 0 (p<0.05, p<0.01, p<0.03, respectively). Survival was significantly shorter for patients with > or =6 ng/ml sFas serum levels, although a multivariate analysis did not show sFas to be a significant independent prognostic factor. Fresh B-CLL cells showed only low levels of membrane expression, which were not correlated to sFas levels in serum. In vitro activation of B-CLL cells increased Fas expression, as reported earlier, and induced cells to release sFas into the supernatant. In conclusion, our results indicate that sFas in serum may be a useful parameter for the prediction of clinical progression in B-CLL.

Adult↗

PubMed2001

Non-malignant leukocytes delay spontaneous B-CLL cell apoptosis.

Malignant B cells from chronic lymphocytic leukemia (B-CLL) patients have a long survival in vivo, although, in culture, they spontaneously die by apoptosis. Here, we analyzed the capacity of accessory leukocytes to modulate apoptosis of B-CLL cells in vitro. To this end, we performed long-term cultures using total mononuclear cells (TMC) from B-CLL patients and TMC depleted from monocytes, NK cells and T lymphocytes (B-CLL cells). In all the patients studied (n = 25) the presence of accessory leukocytes markedly prolonged the survival of B-CLL cells. The anti-apoptotic effect was exerted by monocytes and, to a lesser degree, NK cells, partially through the release of soluble factors. Indeed, accessory leukocytes separated from leukemic cells by semipermeable membranes were still able to prolong B-CLL cell survival. By flow cytometric analysis we found that the protective effect of non-malignant cells was associated with delayed down-regulation of Bcl-2 expression on leukemic cells. By contrast, the expression of Fas and Fas ligand proteins was unchanged in most samples. Our findings suggest that monocytes and NK cells, by delaying leukemic cell apoptosis, may play a role in B-CLL cell accumulation in vivo.

Aged↗

PubMed2005

VEGF receptors on chronic lymphocytic leukemia (CLL) B cells interact with STAT 1 and 3: implication for apoptosis resistance.

We have previously shown that chronic lymphocytic leukemia (CLL) B cells secrete vascular endothelial growth factor (VEGF) in vitro, have constitutively active VEGF receptors R1 and R2, and respond to exogenous VEGF by specifically upregulating Mcl-1 and XIAP in association with decreased cell death. We found that epigallocatechin (EGCG) decreases VEGF receptor phosphorylation and induces apoptosis in CLL B cells. The mechanism(s) by which VEGF receptor activation increases Mcl-1 and XIAP and promotes survival remains unknown. To further define the signaling pathway mediating VEGF induction of antiapoptotic proteins in CLL B-cells, we investigated downstream effects of VEGF-VEGF receptor binding on the STAT signaling pathway. We find that CLL B cells abundantly express cytoplasmic serine phosphorylated (p)-STAT-1 and p-STAT-3, VEGF-R1/2 are physically associated with p-STAT-1 and p-STAT-3, and p-STAT-3 (but not p-STAT-1) is found in the CLL nucleus. VEGF receptor ligation selectively induces activation and perinuclear translocation of STAT 3 through receptor-mediated endocytosis. The inhibition of VEGF receptor activation with either tyrosine kinase inhibitors or VEGF neutralizing antibodies inhibit VEGF receptor phosphorylation, decrease p-STAT-3 (serine 727), Mcl-1, and induces cell death in CLL B cells. Thus, a VEGF-VEGF receptor pathway in CLL B cells can be linked to activation of STAT proteins that are able to enhance their apoptotic resistance.

Apoptosis↗

PubMed2004

Allelotyping in B-cell chronic lymphocytic leukemia (B-CLL).

B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous malignant disease, both in terms of molecular abnormalities and clinical course. The most frequent chromosomal aberrations in B-CLL are deletions on 13q, 11q, and 17p, and trisomy 12, all of which are of prognostic significance. These aberrations can be detected by conventional cytogenetic analysis and fluorescence in situ hybridization (FISH), but cytogenetics are hampered by the low mitotic index of B-CLL cells, and FISH depends on genetic information of candidate regions. Microsatellites are unique highly polymorphic and informative genetic markers dispersed in the human genome. They have become the most commonly used markers to trace loss of heterozygosity in tumors. Their detection by PCR is rapid and can be semi-automated with maximal robustness and reproducibility. In this review, we discuss the implications of a recent genome-wide analysis in B-CLL with 400 microsatellite markers. This analysis led to the detection of new aberrant loci in B-CLL which are not visible in the leukemic conventional karyotype. We conclude that microsatellite allelotyping provides a complementary comprehensive view of genetic alterations in B-CLL, and it may identify new loci with candidate genes relevant in the molecular biology of B-CLL.

Alleles↗

PubMed2004

Fludarabine-induced apoptosis in CD19+/CD5+B-CLL cells is a direct and nurse-like-cell independent effect.

B-cell chronic lymphocytic leukemia (B-CLL) is a hematological malignancy characterized by the accumulation of mature CD5+ B lymphocytes with a defective apoptosis. A subset of blood monocyte-derived adherent cells generated in vitro protects B-CLL cells from apoptosis playing a role as nurse-like cells (NLCs). Fludarabine (9-beta-D-arabinofuranosyl-2-fluoroadenine; F-ara-A) is an adenine nucleoside analog used to treat B-CLL. To gain insight into the mechanisms implicated in the antitumoral effect of fludarabine in B-CLL cells, we performed cross-cultures with B-CLL cells and NLCs treated and untreated with fludarabine. Our results showed that fludarabine blocked the development of NLCs and induced apoptosis in these cells when they were present in culture. Moreover, CD19+/CD5+B-CLL cells treated with fludarabine underwent apoptosis and this event was not related with the presence of NLCs whether treated or not with fludarabine. In conclusion, apoptosis induced by fludarabine in CD19+/CD5+B-CLL cells was due to a direct effect on these cells and not due to its effect in the NLCs.

Aged↗

PubMed2004

Microenvironmental interactions and survival of CLL B-cells.

Chronic Lymphocytic Leukemia (CLL) B cells display characteristics consistent with a defect in programmed cell death (apoptosis) and exhibit prolonged survival in vivo. When recovered from peripheral blood or lymphoid tissues from the patient and cultured in vitro, these malignant cells rapidly undergo spontaneous apoptosis. This observation suggests that the selective survival advantage enjoyed by CLL B-cells is not entirely autonomous, raising the possibility of manipulating CLL B-cell survival by iatrogenic means. The extended survival of the neoplastic B-cells creates a permissive soil on which oncogene activation, genetic instability and accumulation of gene mutations favoring disease progression can occur. In addition, such survival-promoting microenvironments can rescue leukemia cells from cytotoxic therapy, giving way to disease relapse. Survival of CLL B-cells is influenced by interactions with non-leukemia cells in the microenvironment of lymph nodes, marrow and other tissues. CLL B-cells have developed many different ways to escape undergoing apoptosis. These include: (a) expression of survival receptor as well as their ligands, giving rise to autocrine survival pathways which are leukemia cell specific; (b) defects in plasma membrane receptor cell signaling, triggered by death receptors such as Fas- and TRAIL; and (c) constitutively active survival signaling pathways such as NFkappaB and PI3K/Akt. Here we discuss some of the molecular mechanisms by which interaction with other cells and factors in the microenvironment provides survival advantages to CLL B-cells in specific in vivo niches, and we suggest some strategies for overcoming these anti-apoptotic mechanisms for improving treatment of CLL.

Animals↗

PubMed1989

Heterogenous response of B cell chronic lymphocytic leukaemia (B-CLL) cells to anti-human IgM antibody (anti-mu) and B cell stimulatory factor 1 (BSF-1).

B cell chronic lymphocytic leukaemia (B-CLL) cells from seven patients were examined for 3H-TdR uptake with anti-human IgM antibody (anti-mu) and B cell stimulatory factor 1 (BSF-1)/IL-4. B-CLL cells from one patient could proliferate with anti-mu plus BSF-1, but not with BSF-1 alone. B-CLL cells from two patients responded to BSF-1 alone; one could proliferate more by adding anti-mu, but the proliferation of the other cells was inhibited by adding anti-mu. On the other hand, B-CLL cells from the other four patients responded neither to anti-mu nor to anti-mu plus BSF-1. Surface densities of membrane IgM of B-CLL cells were also analysed by fluorescence activated cell sorter (FACS), but there was no correlation between proliferative response (DNA synthesis) of B-CLL cells to anti-mu and densities of surface membrane IgM. These results show that there is a functional heterogeneity of B-CLL cells with regard to proliferative response to anti-mu and BSF-1.

Aged↗

PubMed1989

Prognostic factors in chronic lymphocytic leukaemia: the importance of age, sex and response to treatment in survival. A report from the MRC CLL 1 trial. MRC Working Party on Leukaemia in Adults.

We report the analysis of prognostic factors in a cohort of 660 patients entered in the first Medical Research Council trial in chronic lymphocytic leukaemia (CLL) between 1978 and 1984. The majority (94%) of patients were aged 50 or over and the number of men (M) was almost twice that of women (F) with an M:F ratio of 1.8:1. The M:F ratio was lower, 1.5:1, in patients aged 70 or over. Stage A CLL was the most common, and stage C the least common, among women of all ages, in contrast to men for whom stage A only predominated in the older age group. As the majority of CLL patients are elderly we have examined the causes of death in great detail. 29% of deaths were unrelated to CLL, mainly other cancers (12%) and cardiovascular complications (16%). The majority of deaths in patients presenting with stages B and C were from CLL-related causes, whilst almost half of the deaths in patients presenting with stage A were not obviously related to CLL. Univariate analysis disclosed that the A, B, C staging system was the most important factor considered; stratified and multivariate analysis showed that age and response to treatment were the main prognostic factors after stage. Women always fared better than men and this was independent of stage and age. This and other features documented in the trial suggest a major biological difference between the sexes which has not been widely recognized. The significant influence of treatment response on patients' survival suggests that the search for better treatments in CLL may be rewarding. The improved median survival of stage C patients recorded in this trial, 41 months, compares favourably with previous reports and may have resulted from better treatment.

Age Factors↗