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Biomedical subjects

D M Knowles

Publications and source records attributed to D M Knowles.

At least 91 records · Page 5Linked to original sources
PubMed1993

Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma.

The molecular pathogenesis of diffuse large-cell lymphoma (DLCL), the most frequent and clinically relevant type of lymphoma, is unknown. A gene was cloned from chromosomal translocations affecting band 3q27, which are common in DLCL. This gene, BCL-6, codes for a 79-kilodalton protein that is homologous with zinc finger-transcription factors. In 33 percent (13 of 39) of DLCL samples, but not in other types of lymphoid malignancies, the BCL-6 gene is truncated within its 5' noncoding sequences, suggesting that its expression is deregulated. Thus, BCL-6 may be a proto-oncogene specifically involved in the pathogenesis of DLCL.

Amino Acid Sequence↗
PubMed1993

Mutational activation of N- and K-ras oncogenes in plasma cell dyscrasias.

The frequency of N- and K-ras oncogene mutations was investigated in plasma cell dyscrasias. Genomic DNAs from 128 patients were selected for this study: 30 monoclonal gammopathies of undetermined significance, 8 solitary plasmacytomas, 77 multiple myelomas (MM), and 13 plasma cell leukemias (PCL). A two-step experimental approach was devised. All samples were screened for mutations by single-strand conformation polymorphism analysis. DNA fragments displaying an altered electrophoretic mobility were further studied by direct sequencing to confirm and characterize the nature of the mutations. Ras mutations are not randomly distributed because they are detectable only in MM (9%) and PCL (30.7%). N-ras codons 12, 13, and 61 and K-ras codon 12 were found to be mutated, but N-ras codon 61 mutation was the most frequent finding (63.6%). In conclusion, ras mutations were found in PCL, and in a subset of MM characterized by advanced-stage disease and adverse prognostic parameters. Furthermore, based on our findings, it is possible to speculate that ras mutations represent a late molecular lesion in the process of multistep carcinogenesis.

Base Sequence↗
PubMed1993

Multiple genetic lesions in acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma.

Non-Hodgkin's lymphoma (NHL) develops in about 5% to 10% of acquired immunodeficiency syndrome (AIDS) patients. The vast majority of AIDS-NHL are clinically aggressive B-cell NHL that are histologically classified as small noncleaved cell lymphoma (SNCCL), large cell immunoblastic plasmacytoid lymphoma (LC-IBPL), and large noncleaved cell lymphoma (LNCCL). In an attempt to understand the molecular pathogenesis of these tumors, we have investigated the involvement of dominantly acting oncogenes (c-myc, N-, K-, H-Ras), tumor suppressor genes (p53, RB1), and Epstein-Barr virus (EBV) infection in 27 AIDS-NHL samples (16 SNCCL, 5 LC-IBP, and 6 LNCCL). The following lesions were detected in AIDS-NHL: EBV infection (10/24; 41.6%), c-myc rearrangement (19/24; 79.1%), Ras mutation (4/27; 14.8%), and p53 loss/mutation (10/27; 37.0%). These lesions are not uniformly distributed, but, rather, cluster with specific types of AIDS-NHL: EBV infection is preferentially associated with LC-IBPL (4/4; 100%), while it is present in only a fraction of SNCCL (5/16; 31.2%) and LNCCL (1/4; 25%); c-myc oncogene activation clusters with SNCCL (16/16; 100%), whereas it is less frequent in LC-IBPL (1/4; 25%) and LNCCL (2/4; 50%); p53 inactivation is restricted to SNCCL (10/16; 62.5%) and consistently associated with c-myc activation. These data show that AIDS-NHL are associated with multiple genetic lesions that involve both proto-oncogenes and tumor suppressor genes and may accumulate in the relatively short period of time (4 to 6 years) between human immunodeficiency virus infection and AIDS-NHL development. These genetic lesions differ in the various AIDS-NHL subtypes, suggesting the involvement of distinct molecular pathway.

Adult↗
PubMed1993

Management of lymphoproliferative disorders after cardiac transplantation.

We conducted a retrospective study of 516 cardiac recipients who underwent transplantation between April 1983 and April 1992, 19 of whom had development of post-transplantation lymphoproliferative disorders (PTLDs). These 19 patients presented with involvement of lung (5), gastrointestinal tract (5), disseminated disease (6), and adenoids and lymph nodes (3). B-cell proliferations ranging from an atypical hyperplasia to malignant lymphoma developed in 18 patients, and mixed cellularity Hodgkin's disease developed in 1 patient. The 19 patients with PTLD displayed a predominance of both women and cardiomyopathy as the indication for transplantation when compared with two separate control populations. No correlation was found between demographic criteria analyzed and (1) early versus late diagnosis of PTLD after transplantation, (2) the site of PTLD involvement, or (3) the histopathologic category of the PTLD lesion. Patients with gastrointestinal tract and lung PTLD involvement enjoyed an improved survival after both transplantation and PTLD diagnosis when compared with patients with PTLD involvement of all other extranodal sites. We report a high incidence of PTLD involving the lung and gastrointestinal tract in our cohort study. These sites of involvement responded better to a reduction in immunosuppression than did the other extranodal sites of involvement.

Adult↗
PubMed1993

Biologic aspects of AIDS-associated non-Hodgkin's lymphoma.

Acquired immunodeficiency syndrome-associated non-Hodgkin's lymphomas represent a significant and formidable clinical problem. They also represent an important biologic model for investigating the development and progression of high-grade malignant lymphomas and for studying lymphomas that develop in the setting of immune deficiency. A vast majority of non-Hodgkin's lymphomas exhibit clonal immunoglobulin gene rearrangements and, hence, are B-cell neoplasms. Most express B-cell phenotypes, but a minority, predominantly body cavity-based tumors, express indeterminate phenotypes. AIDS-associated non-Hodgkin's lymphomas do not contain HIV. However, approximately 40% of systemic non-Hodgkin's lymphomas, predominantly those with immunoblastic plasmacytoid morphology, and essentially 100% of primary central nervous system AIDS-associated non-Hodgkin's lymphomas contain Epstein-Barr virus. The c-myc protooncogene is rearranged in approximately 80% of systemic cases, predominantly in those with Burkitt's and Burkitt's-like morphology. Point mutations of the ras gene are detectable in approximately 15% of systemic cases. The p53 tumor-suppressor gene is mutated in approximately two thirds of systemic AIDS-associated Burkitt's and Burkitt's-like non-Hodgkin's lymphomas. The retinoblastoma tumor-suppressor gene does not appear to be mutated or deleted in AIDS-associated non-Hodgkin's lymphomas. In summary, various genetic lesions occur in AIDS-associated non-Hodgkin's lymphomas, which appear to vary according to the anatomic site of disease (systemic vs central nervous system vs body cavity) and the histopathology (Burkitt's vs immunoblastic vs large cell). Further active investigation is necessary to determine the role of these and possibly other genetic lesions in AIDS lymphomagenesis.

Genes, Tumor Suppressor↗
PubMed1993

Down-regulation and desensitization of the beta-adrenergic receptor system of human lymphocytes after cardiac surgery.

We used the beta-adrenergic receptor (beta AR) system of human lymphocytes as a model to examine perioperative adrenergic regulation in 12 patients undergoing coronary artery bypass grafting and 12 patients undergoing mitral or aortic valve replacement. beta AR function was assessed by measuring cyclic adenosine monophosphate (cAMP) production in the unstimulated state and in response to maximal stimulation by isoproterenol and prostaglandin E1. Receptor number and dissociation constant (KD) were assessed with [125I]iodopindolol. In the valve surgery patients, basal, isoproterenol-stimulated, and prostaglandin E1-stimulated cAMP production were significantly decreased postoperatively, by 39%, 55%, and 24%, respectively. beta AR number decreased from a mean of 1333 +/- 143 sites/cell to 897 +/- 56 sites/cell postoperatively, whereas the KD increased from 12.9 +/- 1.1 pM to 37.0 +/- 7.3 pM. In the coronary artery bypass graft patients, there were no significant alterations in cAMP production or receptor number, but the KD increased from 19.8 +/- 2.9 pM to 57.5 +/- 11.8 pM. These findings suggest that cardiac surgery and/or cardiopulmonary bypass may result in significant down-regulation and desensitization of the beta AR system of lymphocytes, which may parallel alterations in other organ systems.

Aged↗
PubMed1993

High levels of p53 protein expression do not correlate with p53 gene mutations in anaplastic large cell lymphoma.

Strong immunohistochemical reactivity for p53 tumor suppressor gene product has been reported in a variety of different human malignancies including CD30- (Ki-1) positive anaplastic large cell lymphoma (ALCL). Although high levels of p53 protein have been interpreted as abnormal, rapidly proliferating benign and neoplastic lymphoid cells may have increased p53 expression in the absence of structural alterations. On the other hand, mutations in the p53 gene can lead to a lack of p53 protein production. Structural alterations of the p53 gene have not been documented in cases of ALCL and the mechanism for an abnormal pattern of p53 expression in these lymphomas has not been elucidated. Therefore, to determine whether an altered pattern of p53 expression correlates with mutations in the p53 locus in ALCL, we analyzed the expression of p53 protein immunohistochemically, compared it with the proliferation index using monoclonal antibody Ki-67, and assessed the presence of mutations in exons 5 though 9 of the p53 gene using a single-strand conformation polymorphism assay in a panel of 17 ALCLs. Furthermore, we studied the presence of allelic deletions of chromosome 17p by restriction fragment length polymorphism analysis. We found significant levels of p53 protein expression in 12 of the 15 cases studied, but identified mutations in only one of 17 cases. An allelic deletion in chromosome 17p was identified only in the one case containing a mutated p53 gene. Whereas the case containing structural alterations in the p53 gene did have strong p53 immunoreactivity, 11 cases that lacked p53 mutations in the regions examined also had significant levels of p53. Thus, our studies indicate that strong immunohistochemical reactivity for p53 is not a reliable indicator of the presence of structural alterations of p53 gene exons 5 through 9 in ALCL.

Adolescent↗
PubMed1993

Immunophenotypic and immunogenotypic approaches useful in distinguishing benign and malignant lymphoid proliferations.

Distinguishing benign and malignant lymphoproliferative disorders by purely morphologic criteria can be difficult. Immunophenotypic analysis is a useful adjunct to the morphologic evaluation of lymphoproliferative disorders and is of considerable assistance in resolving difficult diagnostic dilemmas. Immunophenotypic analysis can be performed on virtually any pathologic specimen using a variety of methodologic approaches. The analysis should be tailored to the individual pathologic specimen and the specific diagnostic problem. The results should be correlated with the clinical and morphologic findings. Southern blot hybridization analysis of the antigen receptor genes has proven to be an objective, accurate, and sensitive method by which to determine the lineage and clonality of lymphoid proliferations and to detect clonal B- and T-cell populations that are not recognizable morphologically or immunophenotypically. Polymerase chain reaction-based strategies extraordinarily more sensitive than Southern blotting are currently being developed. However, the demonstration of clonal antigen receptor gene rearrangements is an indication of clonality and not necessarily of malignancy, although the two are closely related. This and all the other biologic and technical limitations of immunogenotypic analysis must be considered when evaluating the results of such studies. Ideally, the results of immunogenotypic analysis should be interpreted only in conjunction with the results of morphologic evaluation and immunophenotypic analysis.

Antibodies, Monoclonal↗
PubMed1993

In vitro establishment of AIDS-related lymphoma cell lines: phenotypic characterization, oncogene and tumor suppressor gene lesions, and heterogeneity in Epstein-Barr virus infection.

Lymphoma represents a major source of morbidity and mortality among AIDS patients. AIDS-associated non-Hodgkin lymphomas (AIDS-NHL) are almost invariably B-cell derived, are classified as high or intermediate grade lymphomas, and display three main histologic types: namely, small non-cleaved cell lymphoma (SNCCL), large cell immunoblastic plasmacytoid lymphoma (LC-IBPL), and large cell lymphoma (LCL). Here we report the in vitro establishment of three new AIDS-NHL cell lines (termed HBL-1, HBL-2, and HBL-3) derived from three AIDS-SNCCL patients differing in primary tumor sites and risk factors for HIV infection. The derivation of the cell lines from the original tumor clones was established by immunophenotypic and molecular genetic analysis. These cell lines display clonal immunoglobulin gene rearrangement, express surface immunoglobulin and B-cell restricted markers, and exhibit a phenotype consistent with SNCCL. Monoclonal Epstein-Barr virus infection was found in only one of the cell lines (HBL-1). Cytogenetic analysis demonstrated the presence of a chromosomal translocation involving the c-myc proto-oncogene and an immunoglobulin locus in all three cell lines. The pattern of genetic lesions detected in HBL-1, HBL-2, and HBL-3 reflects that found in primary AIDS-SNCCL and includes activation of the c-myc oncogene as well as inactivation of the p53 tumor suppressor gene. These cell lines should prove useful in studies of the biological, immunological, and viral factors involved in AIDS-associated lymphomagenesis.

Adult↗
PubMed1993

Detection of immunoglobulin gene rearrangement of B cell non-Hodgkin's lymphomas and leukemias in fresh, unfixed and formalin-fixed, paraffin-embedded tissue by polymerase chain reaction.

BACKGROUND: The majority of B cell nonHodgkin's lymphomas (NHLs) are composed of a genotypically identical cell population characterized by a unique immunoglobulin (Ig) VDJ gene rearrangement which is customarily documented by Southern blot hybridization analysis of fresh tissue. Sometimes, however, this approach cannot be used because of an insufficient quantity of tissue or the unavailability of fresh tissue. Therefore, alternative strategies should be designed in order to overcome these limitations. EXPERIMENTAL DESIGN: One possible alternative is the identification of Ig VDJ products of normal and neoplastic B cells by polymerase chain reaction (PCR) using mixed oligonucleotide primers recognizing the framework III region or Ig variable heavy chain leader sequences and universal Ig heavy chain joining region (JH) oligonucleotide primers. To determine whether the respective DNA samples are suitable for PCR amplification, control and unrelated genes should also be investigated (exon 5 of the p53 gene). In this study, genomic DNA was extracted from a well characterized panel of 139 human B cell lymphoid leukemias and NHLs derived from fresh (84) and/or paraffin-embedded (55) tissue, 19 normal peripheral lymphoid tissues, 9 Epstein-Barr virus infected lymphoblastoid cell lines and, as negative controls, 11 T cell LLs. Clonal Ig gene rearrangement products were assessed for the presence of a distinct PCR fragment after framework III-JH PCR amplification and electrophoretic separation and by DNA sequencing of the cloned PCR-Ig fragments. RESULTS: Eighty-eight of the 139 (63%) B-NHLs consisting of 53/84 (63%) fresh, unfixed and 35/55 (64%) formalin-fixed, paraffin-embedded samples, exhibited distinct PCR bands. Using this approach we were able to identify a single clonal B cell population mixed with 1,000 nonB cells or 5 polyclonal B cells. There was no difference in the detection of monoclonality among different B-NHL categories. PCR fragments were not identified in any of 27 normal lymphoid tissues or 11 T-lymphoid leukemias. To detect a larger number of Ig gene rearrangement products, genomic DNA of 12 B-NHL/lymphoblastoid cell lines were investigated using VH-specific leader and JH oligonucleotides by PCR. A single PCR product was obtained in 9 of 12 (75%) cases and their clonality was documented by DNA sequencing of the cloned PCR fragments. The clonality of 11 of the 12 (92%) cases could be demonstrated using both PCR approaches. CONCLUSIONS: Our results suggest that the monoclonality of human neoplastic B cells can be efficiently evaluated by PCR equally well from fresh, unfixed and formalin-fixed, paraffin-embedded tissues. This technique should prove to be a powerful tool in clinical diagnosis and research as well as in the retrospective analysis of archival pathologic specimens.

Base Sequence↗
PubMed1992

Molecular interactions mediating T-B lymphocyte collaboration in human lymphoid follicles. Roles of T cell-B-cell-activating molecule (5c8 antigen) and CD40 in contact-dependent help.

In lymphoid follicles, CD4+ T lymphocytes provide contact-dependent stimuli to B cells that are critical for the generation of specific antibody responses in a process termed Th function. The CD4+ T cell-restricted surface activation protein, 5c8 Ag (T-BAM), has recently been shown to be a component of the contact-dependent helper signal to B cells. To further dissect this process, we utilized a Jurkat T cell lymphoma clone, termed D1.1, that constitutively expresses T-BAM and activates peripheral B cells to express surface CD23 in a contact-dependent mechanism that is inhibited by mAb anti-T-BAM (5c8). Similar to its effect on peripheral B cells, Jurkat D1.1 activates B cells from lymphoid organs, as well as a B cell lymphoma clone, RAMOS 266,4CN 3F10 (RAMOS 266), to up-regulate surface CD23. Interestingly, mAb to the B cell surface molecule, CD40 (mAb G28-5 and B-B20), inhibit D1.1 induced activation of RAMOS 266 and peripheral and lymphoid B cells. In contrast, mAb to CR2 or the adhesion molecules, LFA1, LFA3, or ICAM-1, have little effect. The inhibitory effect of anti-CD40 mAb on B cell activation induced by D1.1 is specific because anti-CD40 potentiates, rather than inhibits, the up-regulation of CD23 on B cells induced by rIL-4. Moreover, cross-linking CD40 molecules by anti-CD40 mAb bound to Fc gamma RII+ (CD32) L cells induces B cell CD23 expression. In vivo, T-BAM-expressing cells are CD4+ T cells that are restricted to lymphoid organs and are localized in the mantle and centrocytic zones of lymphoid follicles and the spleen periarteriolar lymphoid sheath in association with CD40+ B cells. Taken together, these data demonstrate that T-BAM on T cells and CD40 on B cells are involved in contact-dependent T-B help interactions that occur in lymphoid follicles.

Antigens, CD↗
PubMed1992

Structural and functional analysis of oncogenes and tumor suppressor genes in adult T-cell leukemia/lymphoma shows frequent p53 mutations.

The human T-cell lymphotropic virus type I (HTLV-I) is capable of inducing adult T-cell leukemia/lymphoma (ATLL). However, the long latency period between infection and development of ATLL, as well as the small fraction of the infected population that actually develops this disease, suggest that additional factors are involved in its pathogenesis. Therefore, we performed a molecular analysis of 10 cases of ATLL presenting in a nonendemic area that were shown to have HTLV-I sequences by polymerase chain reaction as well as clonal T-cell receptor beta gene rearrangements. We analyzed these cases for alterations in some of the oncogenes and tumor suppressor genes frequently involved in hematopoietic neoplasia. Specifically, we used a single-strand conformation polymorphism assay to determine the presence of mutations in the p53 tumor suppressor gene, as well as the K-RAS, N-RAS, H-RAS, and c-myc oncogenes. In addition, we studied the c-myc gene for rearrangements by Southern blotting and assessed expression of the retinoblastoma (Rb) and p53 genes by immunostaining. Analysis of the c-myc gene and the RAS family of oncogenes did not show any alterations. Also, the Rb gene was expressed in all cases analyzed. However, we found mutations of the p53 gene in 3 of the 10 cases and these results were confirmed by sequence analysis. In two of these cases, we showed by restriction fragment length polymorphism analysis of chromosome 17p sequences that the p53 mutations were accompanied by a loss of heterozygocity. Also, these mutations correlated with an altered pattern of p53 expression. Thus, mutations in the p53 locus may be a cofactor for the development of ATLL in some cases, whereas the c-myc, Rb, and RAS genes do not appear to be involved in these neoplasms.

Alleles↗
PubMed1992

Determination of the DNA content of the Reed-Sternberg cell of Hodgkin's disease by image analysis.

The nature of the Reed Sternberg (RS) cell, the malignant cell of Hodgkin's disease (HD), remains unknown. Cytogenetic studies have yielded ambiguous results regarding the chromosomal profile of this cell. In an attempt to further clarify the ploidy status of the RS cell, we analyzed the DNA content of CD30-positive RS cells and RS cell variants in HD lesions from 32 patients using an image analysis system. A diploid and/or near-diploid (DNA index [DI], 1.0 +/- 0.2) and a tetraploid (2.0 +/- 0.2) RS cell population were identified in 9 and in 11 of the 32 cases examined, respectively. An aneuploid RS cell population was identified in 8 of the 32 cases examined. The remaining four cases contained two RS cell subpopulations with different DNA content, each one representing more than 15% of the total RS cell population. There was no significant correlation between the DNA content of the RS cells and the category of HD. Furthermore, analysis of multiple biopsies of an individual patient taken from different lymphoid organs at the same or different time periods showed a constant DNA profile. Our data indicate that RS cells can express variable DNA content and suggests that multiple subpopulations of RS cells with different DNA content may simultaneously coexist within the same HD lesion in some patients. In addition, the RS cell population within each patient appears to express a specific DNA content profile, possibly representing unique clones. These highly individualized profiles potentially may be useful as markers to follow the clinical course of patients with HD.

Adolescent↗
PubMed1992

Deletions involving two distinct regions of 6q in B-cell non-Hodgkin lymphoma.

The recurrent loss of genetic material from a specific chromosomal region in a given tumor type suggests the presence of a tumor-suppressor gene, the loss or inactivation of which may be relevant for tumorigenesis. In this study, we provide molecular evidence for the recurrent association between deletions on the long arm of chromosome 6 and B-cell non-Hodgkin lymphoma (B-NHL). Normal and tumor DNAs from 71 cases of B-NHL were studied for loss of constitutional heterozygosity (LOH) at 19 loci on chromosome 6 using a panel of restriction fragment length polymorphism (RFLP) probes. LOH, indicating deletion of all or part of 6q, was detected in 16 of 71 cases (22.5%), ranging from low-grade to high-grade B-NHL. The isolated loss of 6p or the loss of other chromosomes (8, 17, 22) tested as controls for specificity was not observed in any case. Comparison of the extent of the deletions among different cases allowed the identification of two distinct regions of minimal deletion (RMD) at 6q25 to 6q27 (RMD-1) and at 6q21 to 6q23 (RMD-2), respectively, suggesting the existence of two tumor-suppressor genes. These data support a role for 6q deletions in B-NHL pathogenesis and provide a basis for identifying the corresponding tumor-suppressor genes.

Biopsy↗
PubMed1992

T-cell chronic lymphocytic leukemia. Unusual morphologic, phenotypic, and karyotypic features in association with light chain amyloidosis.

BACKGROUND: Lymphocytes that display a phenotype of mature B-cells, T-cells, natural killer (NK) cells, or a combination of T-cells and NK cells can be found in patients with lymphoproliferations that manifest as expansions of peripheral blood lymphocytes (PBL). If these PBL expansions exhibit clonality, they can be classified as chronic lymphocytic leukemia (CLL). METHODS/RESULTS: A patient who had two simultaneous, clonal lymphoproliferative disorders manifested as an unusual T-cell CLL in conjunction with systemic light chain amyloidosis is described. Gene rearrangement studies of the PBL of the patient showed clonal rearrangements of both the T-cell receptor beta (T beta) chain and the immunoglobulin genes. Additional immunologic and microscopic studies of the T-cells of the patient showed that they were large, agranular, CD4+ T-cells that also expressed the NK cell marker CD57. Cytogenetics disclosed an unusual karyotype in the PBL. CONCLUSIONS: The pathogenesis of this T-cell CLL and whether it truly represents a malignant disorder, as well as its relation to amyloidosis, is discussed.

Aged↗
PubMed1992

Monoclonal antibody OPD4 detects neoplastic T cells but does not distinguish between CD4 and CD8 neoplastic T cells in paraffin tissue sections.

Monoclonal antibody (MoAb) OPD4, reported to preferentially react with benign CD4 T cells in formalin-fixed tissue sections, was examined for its reactivity with 56 T-cell neoplasms after formalin or Bouin's fixation to determine if it also preferentially detects neoplastic CD4 T cells in paraffin tissue sections. Monoclonal antibody OPD4 did not preferentially detect neoplastic CD4 T cells, since it reacted with 22 of 38 (58%) CD4-positive compared with nine of 14 (64%) CD4-negative T-cell neoplasms. However, MoAb OPD4 appears to detect neoplastic T cells in Bouin's-fixed (11 of 20 cases [55%]) about as well as in formalin-fixed (20 of 32 cases [63%]) tissues. Since MoAb OPD4 does not preferentially react with neoplastic CD4 T cells, the utility of this MoAb as a pan-T-cell marker in routinely processed tissues was also explored and compared with that of Leu-22, UCHL-1, and CD3. All four antibodies reacted with approximately the same percentage of T-cell malignancies (51% to 57%). However, examination of different clinicopathologic groups and types of fixative highlighted differences. Monoclonal antibodies OPD4 and Leu-22 reacted with 62%, while CD3 detected only 41% of formalin-fixed, postthymic T-cell neoplasms. OPD4, UCHL-1, and CD3 each reacted with 55%, but Leu-22 recognized only 45% of Bouin's-fixed, postthymic T-cell malignancies. OPD4 reacted with none, but CD3 reacted with all four T-cell lymphoblastic lymphomas. Various antibody combinations were examined to determine an optimal panel for the recognition of T-cell neoplasms in paraffin sections. The combination of MoAbs OPD4 and Leu-22 detected 86% of postthymic T-cell neoplasms in formalin-fixed tissue sections. Furthermore, MoAb OPD4 appears to be relatively specific for T-cell neoplasms, detecting 31 of 56 (55%) T-cell malignancies, while only reacting with two of 39 (5%) B-cell neoplasms. Therefore, while not preferentially reactive with neoplastic CD4 T cells, MoAb OPD4 may be useful as a pan-T-cell marker of postthymic T-cell neoplasms in routinely processed, formalin-fixed tissues, especially when used in conjunction with MoAb Leu-22.

Antibodies, Monoclonal↗
PubMed1992

Neurolymphomatosis: a clinicopathologic syndrome re-emerges.

We describe a patient with sensorimotor peripheral neuropathy and cranial neuropathy due to autopsy-proven neurolymphomatosis defined by infiltration of peripheral nerves by tumor cells and review the findings in 39 previously reported patients. The cause of the neuropathy is not known. The association with immune-deficient states suggests virally mediated pathogenesis, possibly a retrovirus.

Adult↗