About 80% to 90% of females are informative for X- inactivation/methylation analysis with the probe M27 beta, which would therefore seem attractive in assessing clonality in hematologic cell populations. Eighteen acute lymphoid or myeloid leukemias, three chronic lymphocytic leukemias, and three chronic myelogenous leukemias as well as 12 malignant non-Hodgkin's lymphomas mostly showed extremely skewed clonal X inactivation (median allelic cleavage ratio [ACR] of unmethylated/inactive M27 beta alleles was 50, range 1 to 100) or hypermethylation of both alleles. Two lymphomas showed random M27 beta X inactivation but clonal antigen-receptor gene rearrangements. In normal peripheral blood leukocytes from 105 healthy females aged 2 to 96 years, the median ACR was 2 (range 1 to 100). Thus, it was significantly lower than in the leukemias (P = .0001, Mann-Whitney test), but extremely skewed patterns (ACR > 10.8, ie, >80th percentile) were seen not only in the leukemias but also in 21/105 samples (20%) of normal leukocytes, and significantly more frequent in a population of elderly women (aged 75 to 96 years) compared with healthy children (aged 2 to 8 years) and younger women (aged 20 to 58 years) (P =.00125; chi 2 test). We conclude that in a population of cells derived from the hematopoietic system where clonality is uncertain, skewed M27 beta patterns are not reliable indicators for the presence of a clonal neoplastic disorder. The basis for severe X-inactivation skewing is unclear at present, but this finding raises interesting questions regarding the composition of the hematopoietic stem cell pool.
A novel association, Epstein-Barr virus-positive Ki-1+/CD30+ anaplastic large cell non-Hodgkin's lymphoma of B-cell phenotype in immunosuppressed renal transplant recipients is reported. Case 1 involved an aggressive clinical evolution, whereas case 2 followed a more "benign" clinical course. Both lymphomas were Epstein-Barr virus-positive as assessed by in situ hybridization, Southern blot, polymerase chain reaction, and immunohistochemical analysis. Both lymphomas contained a single clonal Epstein-Barr virus terminal-repeat fragment. In case 1, clonality was confirmed by the detection of bi-allelic immunoglobulin (Ig) heavy chain gene rearrangement. Case 2 showed germline Ig genes at presentation and oligoclonal Ig heavy chain gene rearrangements at relapse. These results are consistent with the notion that anaplastic large cell lymphoma might arise in a B cell transformed by Epstein-Barr virus at a very early stage, before Ig gene rearrangement. The latter may occur later in the course of clonal evolution, thus permitting investigators to trace intermediate and late stages within a process of multistep lymphomagenesis and/or tumor progression.
Plasmin-treated human IgG preparations were separated on Sephadex G-100 columns, and proteins of three peaks eluted prior to Fab/Fc fragments were investigated. Determinations of the apparent molecular weight of these peaks revealed that IgG dimers, plasmin-resistant IgG monomers and additional components with a molecular weight of about 115,000 were eluted. IgG subclasses were measured in individual effluent fractions and χ, λ and IgG/Fc antigenic determinants were demonstrated. IgG2 and IgG4 were found to be relatively resistant, IgG1 and IgG3 susceptible for cleavage by plasmin. In the components with a molecular weight 115,000, two fragments were characterized and shown to be similar to the papain IgG1-Fab/c and IgG1-Fc(2) fragments.
About 80% to 90% of females are informative for X- inactivation/methylation analysis with the probe M27 beta, which would therefore seem attractive in assessing clonality in hematologic cell populations. Eighteen acute lymphoid or myeloid leukemias, three chronic lymphocytic leukemias, and three chronic myelogenous leukemias as well as 12 malignant non-Hodgkin's lymphomas mostly showed extremely skewed clonal X inactivation (median allelic cleavage ratio [ACR] of unmethylated/inactive M27 beta alleles was 50, range 1 to 100) or hypermethylation of both alleles. Two lymphomas showed random M27 beta X inactivation but clonal antigen-receptor gene rearrangements. In normal peripheral blood leukocytes from 105 healthy females aged 2 to 96 years, the median ACR was 2 (range 1 to 100). Thus, it was significantly lower than in the leukemias (P = .0001, Mann-Whitney test), but extremely skewed patterns (ACR > 10.8, ie, >80th percentile) were seen not only in the leukemias but also in 21/105 samples (20%) of normal leukocytes, and significantly more frequent in a population of elderly women (aged 75 to 96 years) compared with healthy children (aged 2 to 8 years) and younger women (aged 20 to 58 years) (P =.00125; chi 2 test). We conclude that in a population of cells derived from the hematopoietic system where clonality is uncertain, skewed M27 beta patterns are not reliable indicators for the presence of a clonal neoplastic disorder. The basis for severe X-inactivation skewing is unclear at present, but this finding raises interesting questions regarding the composition of the hematopoietic stem cell pool.
Abstract. Plasmin‐treated human IgG preparations were separated on Sephadex G‐100 columns, and proteins of three peaks eluted prior to Fab/Fc fragments were investigated. Determinations of the apparent molecular weight of these peaks revealed that IgG dimers, plasmin‐resistant IgG monomers and additional components with a molecular weight of about 115,000 were eluted. IgG subclasses were measured in individual effluent fractions and χ, Λ and IgG/Fc antigenic determinants were demonstrated. IgG2 and IgG4 were found to be relatively resistant, IgG1 and IgG3 susceptible for cleavage by plasmin. In the components with a molecular weight 115,000, two fragments were characterized and shown to be similar to the papain IgG1‐Fab/c and IgG1‐Fc2 fragments.
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