Biomedical subjects

H C Kluin-Nelemans

Publications and source records attributed to H C Kluin-Nelemans.

At least 19 recordsLinked to original sources

PubMed1997

Gastric lymphomas compared with lymph node lymphomas in a population-based registry differ in stage distribution and dissemination patterns but not in patient survival.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) originating in mucosa-associated lymphoid tissue (MALT) is supposed to have different clinical behavior from lymph node NHL. To test this hypothesis, the authors compared data of gastric NHL patients with lymph node NHL patients in a population-based registry for differences in clinical presentation and prognosis. METHODS: Data from 1981-1989 on patients with primary gastric NHL (n = 109) and patients with primary lymph node NHL (n = 658) were retrieved from a Dutch population-based NHL registry. Patients were compared for stage distribution, involved sites, and survival. The prognostic value of grading lymphomas according to the malignancy grades of the Working Formulation for Clinical Usage was compared with the value of grading MALT NHLs as either low grade or high grade malignancies. RESULTS: Patients with gastric NHL presented more often with localized disease. Stage IV patients had a higher rate of dissemination to other non-lymph node sites but less frequent localization in the bone marrow. The restricted pattern of dissemination was reflected in a significantly lower recurrence rate for gastric NHL. Gastric NHL patients had significantly better disease free survival than lymph node NHL patients (80% and 44% at 5 years, respectively; P < 0.001). In contrast, overall survival did not significantly differ between the two groups, and it appeared to depend on disease stage. Grading MALT lymphoma as either low grade (26%) or high grade (70%) malignancies did not provide better prognostic information than grading according to the Working Formulation for Clinical Usage (low 8%, intermediate 75%, high 9%). CONCLUSIONS: Primary gastric NHL shows a restricted dissemination pattern, which gives support to the MALT lymphoma concept. Although this might explain the superior disease free survival observed for gastric NHL patients, it does not translate into better overall survival for these patients.

Adult↗

PubMed1997

Human cytotoxic CD8+ T-lymphocyte clones engraft in severe combined immunodeficient (SCID) mice but show diminished function.

Mice with severe combined immunodeficiency (SCID) provide an in vivo model for studying interactions between human tumor cells and effector cells of the immune system. We studied the behavior of human alloreactive cytotoxic T lymphocytes (CTLs) in SCID mice, including the migration pattern of CD8+ or CD4+ CTL clones to various murine tissues, their engraftment in the absence or presence of recombinant human interleukin 2 (rhIL-2) compared with the engraftment of lymphokine activated killer (LAK) cells, and the in vitro as well as the in vivo function of the engrafted CTL clones. The polymerase chain technique using T-cell-receptor-gamma specific primers revealed the presence of human CD8+ CTL clones in the blood, lungs, and liver of mice receiving rhIL-2 for 14 days, for at least 18 days after intravenous inoculation. Human T cells were transiently detected in the bone marrow, lymph nodes, thymus, and spleen. Although the three CD8+ CTL clones and two CTL lines tested required rhIL-2 for their engraftment, the four LAK cell populations also engrafted in the absence of rhIL-2. In contrast to CD8+ T cells, only low frequencies (<1%) of CD4+ cells could be detected in the blood of the SCID mouse. Engrafted human T cells recovered from the murine blood showed absent or diminished cytotoxicity in vitro against human target cells in five or six experiments, respectively. In addition, when the antitumor activity of engrafted CD8+ clones was investigated in vivo using a xenotransplantation model of human B-cell lymphoma in SCID mice, no significant prolongation of the mean survival time of six treated animals was observed compared with animals treated with rhIL-2 alone. Our results illustrate that although in vitro primed and cultured human CD8+ T cells engraft in SCID mice, their in vitro and in vivo function is impaired.

Animals↗

PubMed1996

Direct visualization of dispersed 11q13 chromosomal translocations in mantle cell lymphoma by multicolor DNA fiber fluorescence in situ hybridization.

Several hematologic malignancies are associated with specific chromosomal translocations. Because of the dispersed distribution, chromosomal breakpoints may be difficult to detect using molecular techniques. We present a new application of a recently developed method, DNA fiber fluorescence in situ hybridization (fiber FISH), which allows direct visualization and mapping of chromosomal breakpoints. We tested this method for detection of the t(11;14)(q13;q32) translocation in mantle cell lymphoma. In DNA fiber FISH, a series of fluorochrome-labeled DNA probes covering several hundreds of kilobasepairs is hybridized to linear DNA molecules (or fibers) prepared from frozen tissue or intact cells. By using alternate fluorescent colors, a potential breakpoint region is stained in a color barcode pattern. Breaks in this region will split the barcode in two complementary parts, from which the breakpoint position can be derived. We used a 250-kb barcode covering the BCL-1 locus to detect 11q13 breakpoints in 20 well-characterized mantle cell lymphomas. A t(11;14) was shown by cohybridization of these probes with probes for the Ig heavy chain locus at 14q32. In 18 of 20 mantle cell lymphomas, a breakpoint within the 11q13/BCL-1 barcode was shown by the presence of multiple, complementary translocation products. Fusion of 11q13 and 14q32 sequences on single fibers indicating t(11;14)(q13;q32) was found in all 18 breakpoint-positive mantle cell lymphomas. In one additional case, fusion of an intact 11q13 barcode with 14q32 sequences indicated a breakpoint 100 kb centromeric of the major translocation cluster of BCL-1. Within the 120-kb region of BCL-1, breakpoints were widely scattered. This explains why, so far, a BCL-1 breakpoint had been detected by Southern blot analysis in only 10 of 19 cases. DNA fiber FISH analysis showed a t(11;14) in 95% of mantle cell lymphoma. The results indicate that DNA fiber FISH is a rapid, simple, and equally powerful method for detection of clustered and dispersed translocation breakpoints.

Chromosome Aberrations↗

PubMed1996

AP-1 regulates the basal and developmentally induced transcription of the CD11c leukocyte integrin gene.

The p150,95 integrin (CD11c/CD18) mediates leukocyte/endothelium interactions during inflammatory reactions and certain CTL-target interactions, and is also a receptor for fibrinogen, LPS, and the complement component iC3b. CD11c/CD18 is expressed primarily on cells of the myeloid lineage and activated B lymphocytes, and is an important diagnostic marker for hairy cell leukemia. To identify the transcription factors and cis-acting elements involved in the regulated expression of CD11c/CD18 during myeloid cell differentiation and B lymphocyte activation, we have performed structural and functional analysis on the CD11c gene promoter. Electrophoretic mobility shift assays identified an AP-1 binding site (AP1-60) within the proximal promoter region and evidenced differences in the pattern of the Fos family members bound to the AP1-60 element in undifferentiated and differentiated myeloid cells, as well as between B lineage-derived cells. The involvement of the AP1-60 element in DNA-protein interactions was confirmed by means of in vivo footprinting experiments, and its functionality was demonstrated by trans activation of the CD11c promoter by c-Jun. Site-directed mutagenesis of AP1-60 greatly reduced the basal CD11c promoter activity in myeloid and B cells. Furthermore, mutations at AP1-60 inhibited the induction of the CD11c promoter activity during the PMA-triggered U937 cell differentiation, pointing out a key role for the AP-1 transcription factor complex in both the basal and the developmentally regulated expression of the p150,95 leukocyte integrin. The involvement of AP-1 in the transcription of the CD11c gene raises the possibility of altering leukocyte integrin expression by pharmacologic means and will greatly contribute to the characterization of the intracellular signals controlling the expression of leukocyte adhesion molecules.

Base Sequence↗

PubMed1996

Hb Malmö [beta-97(FG-4)His-->Gln] leading to polycythemia in a Dutch family.

We have examined six individuals from a two-generation Dutch family for a suspected hemoglobin (Hb) abnormality. The propositus presented with polycythemia and complained of persistent weakness, headache, and epistaxis. All family members initially showed a normal Hb-electrophoretic pattern, but on isoelectric focusing, three of them displayed a fast-moving band associated with high packed red cell volumes (PCV) and increased red blood cell count. The Hb mutant was analyzed at the DNA level by specific gene fragment amplification (PCR), followed by direct DNA sequencing, and the mutation was confirmed by restriction enzyme analysis. We found a C-->G transversion (CAC-->CAG) at codon 97 of the beta-chain, which corresponded to the His-->Gln amino acid substitution previously described as Hb Malmö. We report here the clinical history of the patient, the effects of phlebotomy treatment, and the effect of subnormal iron conditions on the erythropoietic recovery after phlebotomy. The mechanism responsible for the induction of the higher oxygen affinity is discussed, as are some aspects concerning the occurrence, pathology treatment, and the genetic risk of Hb variants with high O2 affinity.

Adult↗

PubMed1996

High-dose therapy followed by bone marrow transplantation for relapsed follicular non-Hodgkin's lymphoma. Dutch HOVON Group.

PURPOSE: To analyze whether, in addition to survival, and disease-free survival progression-free interval after transplantation would be longer than the last progression-free interval before transplantation, supporting the argument that high-dose therapy may change the biologic behavior of the disease. PATIENTS AND METHODS: Patients with a poor-risk relapsed follicular NHL were treated with three cycles of doxorubicin 50 mg/m2 and teniposide 60 mg/m2, followed by etoposide 350 mg/m2, cyclophosphamide 60 mg/kg, and TBI and unpurged BMT. RESULTS: Twelve patients were entered in the study. Ten patients fulfilled the criteria for response and underwent transplantation, two of them with an allograft. Nine of ten patients with transplants achieved a complete remission after BMT. One patient died on day 41 due to veno-occlusive disease. The nine patients with transplants who were evaluable for follow-up had a conversion of remission or response duration after transplantation, their progression-free interval after BMT being superior to the last one before BMT with a median of 1044 + days. Overall survival and disease-free survival in the transplant patients after a median follow-up of 1160 days from BMT is 90%. CONCLUSION: High dose chemotherapy followed by stem cell rescue may change the clinical course in follicular non-Hodgkin's lymphoma patients.

Adult↗

PubMed1996

Anti-CD45 and anti-CD52 (Campath) monoclonal antibodies effectively eliminate systematically disseminated human non-Hodgkin's lymphoma B cells in Scid mice.

Severe combined immunodeficient (Scid) mice inoculated with the human (t(14;18)-positive B cell lines DoHH2 and BEVA develop lethal systemically disseminated lymphoma (de Kroon et al., Leukemia 8:1385, and Blood 80 [suppl 1]:436). These models were used to study the therapeutic effect of rat-anti-human CD52 (Campath-1G) or CD45 monoclonal antibodies (mAbs) on systemically disseminated tumor cells and on tumor cells present in solid tumor masses. Both mAbs were effective in inhibiting growth of systemically disseminated malignant cells. When treatment with anti-CD52 or anti-CD45 mAbs at a dose of 30 micrograms/mouse/d for 4 days was started 24 hours after intravenous inoculation of human DoHH2 or BEVA cells, a 3-log kill of tumor cells was observed as measured by prolonged survival. After treatment, surviving animals injected with high numbers of BEVA cells showed tumor masses in liver, kidney, and mesenteric lymph nodes. In contrast to nontreated animals, however, only low numbers of malignant cells were found in peripheral blood, and bone marrow was free of tumor cells. Similarly, after mAb treatment of mice inoculated subcutaneously (sc) with DoHH2 cells, no tumor cells could be found in the bone marrow, and few DoHH2 cells could be detected in the peripheral blood, spleen, liver, kidney, or lung. In contrast, tumor cells present in subcutaneous tumors and axillary lymph nodes were relatively unaffected by mAb therapy. The presence of rat immunoglobulin (Ig) could be demonstrated on surviving tumor cells. The presence of murine macrophages in areas in these tumors that were depleted of DoHH2 cells suggested that the mAb-mediated antitumor effect observed in the Scid mouse model is mediated by cellular mechanisms. Apparently these mechanisms were not sufficient to eliminate the fast-growing tumor cells present in the protected sites. Our results indicate that treatment with anti-CD52 or anti-CD45 mAbs potentially may be useful as adjuvant immunotherapy for systemically disseminated B cell lymphoma.

Animals↗

PubMed1995

Cyclin D1 messenger RNA overexpression as a marker for mantle cell lymphoma.

In mantle cell lymphoma (MCL) a recurrent chromosomal rearrangement, t(11;14)(q13;q32), has been described. Most breakpoints have been detected within the 120 kb BCL-1 region, upstream of the cyclin D1 gene. To evaluate the association between BCL-1 rearrangement and expression of cyclin D1 in lymphoproliferative disorders, we analysed a series of 24 MCL, 56 other B-cell non-Hodgkin's lymphomas (NHL), 28 chronic B-cell leukemias, 18 hematopoietic cell lines and 10 normal lymphoid tissues at the RNA level. Hematopoietic cell lines with a known 11q13 translocation showed high expression of the 4.5 kb cyclin D1 transcript. Three B-cell lines without known 11q13 breakpoint showed low expression. We detected high expression in all (11/11) MCL with and in 11 out of 13 cases of MCL without detectable t(11;14) rearrangement. In three cases with a rearrangement at the 3' end of cyclin D1, two showed overexpression of the 1.5 kb transcript and one expression of an aberrant (3.0 kb) transcript. In other lymphoproliferative disorders, only 5/15 hairy cell leukemias, all without detectable t(11;14), and 5/8 B-cell leukemias suspected to be MCL in leukemic phase showed expression levels comparable to MCL, whereas no or only low expression were observed in 56 cases of other NHL, seven chronic B-cell leukemias and all (10/10) normal lymphoid tissues. Cell sorting experiments on fresh tonsils showed that this low expression was present in normal B-cells and not in T-cells. In contrast to other studies, our data indicate that cyclin D1 is expressed in many lymphoproliferative disorders and normal tissues, albeit at low levels. High levels of expression of cyclin D1 however is restricted to MCL and some hairy cell leukemias. We therefore propose that overexpression of cyclin D1 is a reliable marker for the classification of MCL.

Biomarkers, Tumor↗

PubMed1995

Comparison of CHOP chemotherapy with autologous bone marrow transplantation for slowly responding patients with aggressive non-Hodgkin's lymphoma.

BACKGROUND: High-dose chemoradiotherapy combined with autologous bone marrow transplantation can cure patients with disseminated, aggressive non-Hodgkin's lymphoma in whom first-line chemotherapy has failed. In contrast, cure is rare with second-line chemotherapy. It has been suggested that patients with slow responses to the initial phase of first-line chemotherapy are at high risk for relapse. Therefore, such patients are potential candidates for early bone marrow transplantation. METHODS: To investigate whether patients with slow responses, defined as only a partial response after three courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), would benefit from early transplantation, we conducted a prospective, randomized trial. The early application of high-dose chemoradiotherapy and autologous bone marrow transplantation was compared with the continuation of CHOP therapy for another five courses. Patients with complete responses after three courses of CHOP (fast responses) and patients who responded partially but still had tumor-positive marrow continued with another five courses of CHOP. The study end points were the response rate, overall survival, disease-free survival, and event-free survival. RESULTS: Of 286 patients who could be evaluated for the rapidity of their response after three courses of CHOP, 38 percent had fast responses, 47 percent had slow responses, and 15 percent had no response. Among 106 patients with slow responses who had lymphoma-negative marrow, 69 patients (65 percent) were randomized. Seventy-four percent of the CHOP group and 68 percent of the transplantation group had complete remissions (P = 0.54). At four years the rates of overall, disease-free, and event-free survival were 85, 72, and 53 percent, respectively, in the CHOP group and 56, 60, and 41 percent in the transplantation group (P > 0.10). The disease-free survival in both groups did not differ significantly from that of nonrandomized patients with fast responses (54 percent at four years). CONCLUSIONS: The early application of high-dose, marrow-ablative chemoradiotherapy with autologous bone marrow transplantation does not improve the outcome in patients with aggressive non-Hodgkin's lymphoma that responds slowly to first-line CHOP chemotherapy.

Adolescent↗

PubMed1995

Differentiation of follicular lymphoma cells after autologous bone marrow transplantation and haematopoietic growth factor treatment.

A patient with follicular lymphoma developed a striking but transient plasmacytosis in blood and bone marrow with paraproteinaemia after treatment by autologous bone marrow transplantation and interleukin-3 (IL-3). By immunophenotyping, cytogenetics and Southern blotting, we proved that the plasma cells were clonally related to the original lymphoma cells. This event was preceded by fever accompanied by high IL-6 concentrations. The patient recovered spontaneously and had a long-lasting remission. We speculate that the bone marrow-derived malignant B cells were stimulated by IL-3 and IL-6 into terminally differentiated plasma cells.

Adult↗

PubMed1995

IgD class switching: identification of a novel recombination site in neoplastic and normal B cells.

IgD on normal B lymphocytes usually is co-expressed with IgM. A minority of normal plasma cells and rare B cell malignancies express exclusively IgD (IgM-IgD+). The low frequency has been explained by the lack of a recognizable switch region within the C mu-C delta intron. We analyzed four cases of IgM-IgD+ hairy cell leukemia (HCL) by Southern (DNA) blot analysis and identified two cases with a recombinatorial event within the C mu-C delta intron and deletion of C mu. DNA sequence analysis of junctional regions showed that S mu or the immediate upstream region was used as a donor site and that the C mu-C delta intronic sigma delta region was used as acceptor site. Using polymerase chain reaction, we subsequently analyzed whether similar S mu-sigma delta recombinations occur in normal tonsils containing IgM-IgD+ plasma cells. Multiple products with a size range of 200-800 base pairs were detected in all four individuals, suggesting clustering of acceptor sites within sigma delta. Sequence analysis of three cloned products showed S mu-sigma delta recombinations similar those observed in HCL. The sigma delta region contains a relatively high content of pentameric repeats with an extremely G-rich area and appears to function as a vestigial switch recombination site in normal and neoplastic IgM-IgD+ B cells.

B-Lymphocytes↗

PubMed1994

Proliferation and cytogenetic analysis of hairy cell leukemia upon stimulation via the CD40 antigen.

Using the CD40 system, in vitro proliferation of hairy cell leukemia (HCL) was examined in 43 patients. In this culture system, cells were stimulated by interleukin-4 (IL-4) and anti-CD40 monoclonal antibodies (MoAbs) that were added in soluble form or were cross-linked via their Fc part using Fc gamma RII-transfected mouse fibroblast cells. Proliferation was induced and confirmed by 3H-thymidine incorporation in 14 cases and by the presence of metaphases in 42 cases. 3H-thymidine incorporation showed a heterogeneous pattern: cross-linking of anti-CD40 gave the highest proliferation in 8 cases; in 11 cases, stimulation with anti-CD40 MoAbs alone, without cross-linking also resulted in proliferation; the addition of IL-4 further enhanced 3H-thymidine incorporation in 5 cases, but suppressed this phenomenon in 5 other cases. The CD40 system proved to be very effective in obtaining cytogenetic data. With a success rate of 42 of 43 patients tested, we found clonal abnormalities in 8 cases (19%) and nonclonal abnormalities with involvement of one or two abnormal metaphases in another 7 cases. The chromosomes most frequently involved in the abnormal karyotypes, both structurally and numerically, were chromosomes 5, 7, and 14. By fluorescence-activated cell-sorting analysis of the cultured cells, and by immunophenotypic analysis of metaphase spreads, T-cell growth could be excluded and the HCL-lineage confirmed. Stimulation via the CD40 antigen is an excellent tool for growing hairy cell leukemia cells.

Adult↗

PubMed1994

Homing and antigenic characterization of a human non-Hodgkin's lymphoma B cell line in severe combined immunodeficient (SCID) mice.

The dissemination pattern of a human non-Hodgkin's lymphoma (NHL) B cell line (DoHH2) carrying the t(14;18) translocation was analyzed in severe combined immunodeficient (SCID) mice, using different routes of administration. When engrafted intraperitoneally (i.p.) the DoHH2 cells showed a local infiltration into intra- and retroperitoneal mouse tissues, and disseminated to bone marrow and lymph nodes. In contrast, after subcutaneous (s.c.) or intravenous (i.v.) transfer the DoHH2 cells displayed a hematogenous spread, and disseminated predominantly to hematopoietic and lymphoid organs including bone marrow, peripheral blood, spleen, peripheral lymph nodes, and liver. No involvement of the gut and mesenteric lymph nodes was observed, suggesting a specific homing pattern, bypassing the mucosa-associated lymphoid tissue (MALT). This pattern is reminiscent of the human disease. Phenotypic analysis, cytogenetic analysis, and minor histocompatibility antigen (mHA) typing using mHA-specific cytotoxic T-lymphocyte (CTL) clones performed on the original DoHH2 cell line and on DoHH2 cells recovered from mouse tissue, showed that in vivo passage did not alter the characteristics of the DoHH2 cells. After i.v. administration, the survival time of the SCID mice directly correlated with the number of DoHH2 cells inoculated. This model of dissemination of the DoHH2 cell line may be useful for studying the efficacy of (immunotherapeutic) treatment of human lymphoproliferative disorders in vivo.

Animals↗

PubMed1993

Multiple breakpoints within the BCL-1 locus in B-cell lymphoma: rearrangements of the cyclin D1 gene.

Centrocytic lymphoma (CC) and intermediately differentiated lymphocytic lymphoma (IDL) are B-cell non-Hodgkin's lymphomas composed of lymphocytes presumably derived from follicle mantle cells. In these lymphomas, a specific chromosomal translocation, t(11;14)(q13;q32), has been described. Previous studies suggested an association between t(11;14) chromosomal translocations and BCL-1 rearrangements. To evaluate the association between BCL-1 rearrangements and CC/IDL, Southern blot analysis was performed on a panel of 20 cases of CC/IDL, 22 cases of morphologically similar non-Hodgkin's lymphomas, 11 cases of chronic B-cell leukemias, and 2 cases of myelomas. We used various probes covering a considerable proportion of the 120-kilobase BCL-1 locus, and rearrangements in 50% of CC/IDL (10 of 20) were detected. In CC, all 4 breakpoints were located at the major translocation cluster (MTC). In contrast, in IDL, rearrangements were detected in 3 different cluster regions: 2 cases in the MTC, 2 cases with a breakpoint 24 kilobases outside the MTC, and 2 additional cases with breakpoints found 3 kilobases 5' of the first exon of the PRAD1/CCND1 gene, which is located 120 kilobases outside the MTC. In addition, one leukemia showed a breakpoint 63 kilobases outside the MTC. In all cases, there was comigration of the rearranged 11q13 fragment and the immunoglobulin heavy chain-joining gene complex, indicating a t(11;14)(q13;q32) chromosomal rearrangement. Our results show that Southern blot analysis is helpful to identify CC/IDL, but multiple breakpoints are present over a large region, and therefore, many probes are necessary to cover all breakpoints.

Chromosome Mapping↗

PubMed1993

Somatic pairing of centromeres and short arms of chromosome 15 in the hematopoietic and lymphoid system.

Normal human bone marrow and peripheral blood leukocytes as well as malignant cells from a variety of leukemias and lymphomas, demonstrate somatic pairing of centromeres and p arms of chromosome 15 during interphase. This phenomenon, effected by sequences on the p arm and requiring the intranuclear transport of spatial domains for at least one of the homologs, was not seen in amniotic fluid cells, uterine cervical tissue or in tissue fibroblasts. These studies contribute to the recent evidence of somatic pairing of homologous chromosomes in man and provide support for mobile chromosomal domains in interphase. It appears that sequences on the p arm of chromosome 15, possibly the nucleolar organizing genes, are uniquely important in the maturation of benign and malignant cells of hemato-lymphopoietic origin.

Cells, Cultured↗

PubMed1993

Decrease of memory T helper cells (CD4+ CD45R0+) in hairy cell leukemia.

Patients with hairy cell leukemia (HCL) are prone to opportunistic infections, which suggests an impaired T-cell functioning. To investigate a possible mechanism of such an impairment, we determined the numbers of naive and memory T cells by measuring the expression of CD45R0 on CD4+ and CD8+ T cells in 23 HCL patients. As control, 13 healthy subjects and 13 patients with other chronic B-cell leukemias were studied. In HCL patients with active disease, the percentage of CD4+ CD45R0+ T cells was significantly lower compared to healthy subjects (41% versus 57%, p = 0.01). Also the absolute numbers of CD4+ CD45R0+ T cells were reduced (396 x 10(6)/l versus 615 x 10(6)/l, p = 0.02) compared to healthy subjects, whereas within the CD8+ subset no differences were found. A contrasting elevation of percentages and numbers of CD45R0-expressing T cells (p < 0.0001) was seen in patients with chronic lymphocytic leukemia or leukemic non-Hodgkin's lymphoma. No relationship between CD4+ CD45R0+ and splenectomy, treatment with alpha-interferon or monocyte numbers was found in the HCL population. Despite the fact that the underlying mechanism of the reduced expression of CD45R0 in CD4+ T cells remains unclear, our observations may contribute to the understanding of an impaired T-cell functioning in HCL.

CD4-CD8 Ratio↗

PubMed1993

Hairy cell leukemia: an interphase cytogenetic study.

Malignant cells from 24 cases of hairy cell leukemia were studied by in situ hybridization for evidence of selective aneuploidy using alphoid and satellite probes specific for 16 human chromosomes. Based on these data, hairy cell leukemia appears to be diploid for the chromosomes studied and is a malignancy which displays the phenomenon of pairing of the centromere and p arm of chromosome 15 during interphase.

Centromere↗

PubMed1992

Induction of CD11a/leukocyte function antigen-1 and CD54/intercellular adhesion molecule-1 on hairy cell leukemia cells is accompanied by enhanced susceptibility to T-cell but not lymphokine-activated killer-cell cytotoxicity.

Some B-cell neoplasms, including hairy cell leukemia (HCL), lack expression of the adhesion molecule leukocyte function antigen-1 (LFA-1/CD11a). Additionally, HCL cells express relatively low amounts of intercellular adhesion molecule-1 (ICAM-1/CD54) and may therefore be an inappropriate target for recognition by T cells or lymphokine-activated killer (LAK) cells. We tested whether these molecules were inducible on HCL cells and if induction would lead to enhanced susceptibility to lysis by LAK cells or cytolytic T cells. CD11a expression was induced by incubation with interferon-alpha (IFN-alpha) or interleukin-4. CD54 was induced by culturing the cells irrespectively of the addition of cytokines. Expression of CD11a and CD54 did not enhance susceptibility to either autologous or allogeneous LAK cells. However, induction of these adhesion molecules was accompanied by enhanced susceptibility to lysis by cytotoxic T lymphocyte clones. This lysis could be reversed by the addition of anti-CD11a and anti-CD54 antibodies. Finally, we monitored the expression of CD11a and CD54 on HCL cells from patients during IFN-alpha therapy. In one of four patients monitored, we observed rapid in vivo induction of CD11a and CD54 on the leukemic cells during IFN-alpha therapy. These studies provide a model for studying immunosurveillance in HCL.

Antigens, CD↗