ABSTRACT
OBJECTIVE@#To analyze the correlation between the mutational status of immunoglobulin heavy chain variable (IGHV) gene with the prognosis of patients with Waldenström macroglobulinemia (WM).@*METHODS@#Immunoglobulin heavy chain gene (IGH) clonotypic sequence analysis was carried out to assess the mutational status of IGHV in the blood and/or bone marrow samples from 44 WM patients. The usage characteristics of IGHV-IGHD-IGHJ gene was explored.@*RESULTS@#The most common IGHV subgroup was IGHV3, which was similar to the data from the Institute of Hematology of Chinese Academy of Medical Science. IGHV3-23 (20.45% vs. 15.44%) and IGHV3-74 (11.36% vs. 7.35%) were the main fragments used, which was followed by IGHV4 gene family (15.91% vs. 24.26%). However, no significant correlation was found between the IGHV4 usage and the prognosis of the patients. Should 98% be taken as the cut-off value for the IGHV mutation status, only 5 patients had no IGHV variant, and there was no correlation with the prognosis. Based on the X-tile analysis, 92.6% was re-selected as the cut-off value for the IGHV variant status in such patients. LDH was increased in 26 patients (59.1%) without IGHV variant (P < 0.05), whilst progression-free survival (P < 0.05) and overall survival (P < 0.05) were significantly shorter compared with those with IGHV variants.@*CONCLUSION@#The usage characteristics of IGHV-IGHD-IGHJ in our patients was similar to reported by the Institute of Hematology of Chinese Academy of Medical Science, albeit that no correlation was found between the IGHV4 usage and the prognosis of the patients. Furthermore, 98% may not be appropriate for distinguishing the IGHV variant status in WM patients.
Subject(s)
Humans , Immunoglobulin Heavy Chains/genetics , Multigene Family , Mutation , Waldenstrom Macroglobulinemia/geneticsABSTRACT
Translocations leading to fusions between the immunoglobulin heavy chain gene (IGH) and various partner genes have been reported in B-cell precursor acute lymphoblastic leukemia (B-ALL). However, submicroscopic deletions within IGH in B-ALL have not been rigorously assessed. In this study, we investigated characteristics of IGH submicroscopic deletions, by FISH, in B-ALL with IGH rearrangements. FISH was performed by using commercially available IGH dual-color break-apart rearrangement probes (Abbott/Vysis, Downers Grove, IL, USA; Kreatech, Amsterdam, Netherlands). The study group included seven B-ALL patients with IGH rearrangements, observed by FISH. Among them, two exhibited deletion of the 5' variable region of IGH by FISH. The B-ALL in these two patients included two kinds of abnormal cells; one had an IGH rearrangement without any IGH submicroscopic deletion, while the other had an IGH submicroscopic deletion, which showed that one normal fusion signal and one 3' IGH signal were detected. Thus, submicroscopic deletion of the IGH 5' variable region may have occurred in either the native or rearranged chromosome 14. These findings indicate that B-ALL with IGH rearrangements may be accompanied by submicroscopic deletions of the IGH 5' variable region, which can be detected by FISH. The clinical significance of such deletions is unclear, but the loss of part of the IGH gene in B-ALL warrants further study.
Subject(s)
Adult , Child , Female , Humans , Infant , Male , Middle Aged , Young Adult , Gene Deletion , Gene Rearrangement , Immunoglobulin Heavy Chains/genetics , In Situ Hybridization, Fluorescence , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/geneticsABSTRACT
No abstract available.
Subject(s)
Child , Female , Humans , Bone Marrow/pathology , Burkitt Lymphoma/diagnosis , Chromosomes, Human, Pair 1 , Flow Cytometry , Immunoglobulin Heavy Chains/genetics , Isochromosomes/genetics , Karyotype , Karyotyping , Proto-Oncogene Proteins c-myc/genetics , Republic of Korea , Translocation, GeneticABSTRACT
Chronic lymphocytic leukemia (CLL) was largely considered to be a disease of slow progression, standard treatment with Chlorambucil and having almost similar prognosis. With the introduction of molecular methods for understanding the disease pathophysiology in CLL there has been a remarkable change in the approach towards the disease. The variation in B-cell receptor response and immunoglobulin heavy chain variable region (IGHV) mutation, genetic aberration and defect in apoptosis and proliferation has had an impact on therapy initiation and prognosis. Early diagnosis of molecular variant is therefore necessary in CLL.
Subject(s)
Chromosome Aberrations , Humans , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Variable Region/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Lymphocytosis/diagnosis , Mutation , Prognosis , Receptors, Antigen, B-Cell/genetics , Tumor Suppressor Protein p53/genetics , ZAP-70 Protein-Tyrosine Kinase/geneticsABSTRACT
Introduction: The differential diagnosis of B-cell lymphoproliferative processes remains a challenge for pathologists, dermatologists and oncologists, despite advances in histology, immunohistochemistry and molecular biology. Objective: Evaluate aid and limitations of clonality analysis in the diagnosis of primary cutaneous B-cell lymphomas and B-cell pseudolymphomas. Methods: This study included 29 cases of B-cell lymphoproliferative processes classified as primary cutaneous B-cell lymphomas (13), B-cell pseudolymphomas (6) and inconclusive cases (10) using histology and immunohistochemistry. The clonality analysis was performed by polymerase chain reaction analysis of immunoglobulin light chain and heavy chain rearrangements. Results: DNA quality was shown to be generally poor; eight samples were inadequate for polymerase chain reaction analysis. The results showed monoclonality in eight of the primary cutaneous B-cell lymphomas and polyclonality in four of the B-cell pseudolymphomas. In addition, monoclonality was shown in two of the inconclusive cases by histology and immunohistochemistry, demonstrating the utility of polymerase chain reaction as an ancillary diagnostic tool for primary cutaneous B-cell lymphomas. Discussion: The low quality DNA extracted from these cases demanded the use of an IgH protocol that yielded small fragments and IgK. Both methods used together improved detection. Conclusion: Use of the two protocols, immunoglobulin heavy chain FR3-trad and immunoglobulin light chain-Kappa Biomed protocols for clonality analysis improved diagnostic accuracy.
Subject(s)
Humans , Lymphoma, B-Cell/pathology , Polymerase Chain Reaction/methods , Pseudolymphoma/pathology , Skin Diseases/pathology , Skin Neoplasms/pathology , Diagnosis, Differential , Immunohistochemistry , Immunoglobulin Heavy Chains/genetics , Immunoglobulin kappa-Chains/genetics , Polymerase Chain Reaction/standardsABSTRACT
BACKGROUND: Immunoglobulin heavy chain (IGH) gene rearrangement, 13q14 deletion and trisomy 1q are frequently observed in Korean patients with multiple myeloma. The purpose of our study was to analyze the statistical correlation between chromosomal aberrations and routine laboratory test results as prognostic markers and to evaluate the potential of chromosomal aberrations for the indirect assessment of prognosis in multiple myeloma patients. METHODS: We investigated the prevalence of cytogenetic aberrations in 41 patients with newly diagnosed multiple myeloma. Cytogenetic analysis was conducted by conventional karyotyping and FISH for the presence of IGH/CCND1 translocation, 13q14 deletion, and trisomy 1q using bone marrow aspirates. The records of routine laboratory tests were reviewed and their correlation with cytogenetic abnormalities was investigated. RESULTS: Sixteen (39.0%) of 41 patients had at least one cytogenetic abnormalities in conventional karyotyping or FISH. In FISH analysis of 37 patients, 8 (21.6%) showed positive result for IGH/CCND1 translocation, 8 (21.6%) for trisomy 1q, and 5 (13.5%) for 13q14 deletion. Cytogenetic abnormalities, especially trisomy 1q, were associated with significantly lower hemoglobin level and significantly higher bone marrow plasma cell percentage and beta2-microglobulin level. CONCLUSIONS: Statistical correlation between the presence of trisomy 1q and prognostic markers suggests that the evaluation of trisomy 1q in multiple myeloma patients may be used for the indirect assessment of prognosis in these patients.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Chromosome Aberrations , Chromosomes, Human, Pair 1 , Chromosomes, Human, Pair 13 , Immunoglobulin Heavy Chains/genetics , In Situ Hybridization, Fluorescence , Karyotyping , Multiple Myeloma/diagnosis , Prognosis , Translocation, Genetic , Trisomy/genetics , Biomarkers, Tumor/bloodABSTRACT
A case of intestinal angiocentric T/NK-cell lymphoma in a 58-year-old man is reported. The patient presented initially with panperitonitis because of perforation of sigmoid colon diverticulum. He underwent segmentectomy of involved bowel. Histologically, the intestinal wall showed diffuse infiltration of medium or large size lymphoma cells with angiocentric growth and necrosis. The lymphoma cells were CD56+, CD45RO+, CD3+, CD4-, CD8-, CD20-, and CD30- in paraffin sections with germline configuration of TCR-gamma gene, consistent with T/NK-cell lymphoma. Further staging revealed splenomegaly. Intestinal angiocentric T/NK cell lymphoma represents a distinct etiology of diverticulum with perforation.