[Mutational features of immunoglobulin heavy chain variable region gene in patients with chronic lymphocytic leukemia].

Objective: To investigate the mutational features of the immunoglobulin heavy chain variable region (IgHV) gene in patients with chronic lymphocytic leukemia (CLL) using immunophenotypic and molecular genetic methods. Methods: The laboratory results of 266 CLL patients who underwent IgHV gene examination at Sino-US diagnostics laboratory from February 2020 to February 2021 were analyzed for the IgVH mutational status and presence of specific IgVH fragments. In addition, their immunophenotypic, molecular, chromosomal karyotypic, and FISH profiles were investigated and correlated with the IgVH mutational status. Results: Among 266 patients, 172 were male and 94 were female, with a media age of 67 years (20-82 years).There were more patients with mutated IgHV (m-IgHV) than unmutated IgHV (un-IgHV) (69.2%∶30.8%). There was association of VH family and the presence of gene fragments: the overall incidence of VH families including VH3 family (142/266, 53.4%), VH4 family (75/266, 28.2%), and VH1 family (34/266, 12.8%) was about 95%, among which the proportion of VH4-34 (26/266, 9.8%), VH3-23 (25/266, 9.4%), VH3-7 (24/266, 9.0%), and VH4-39 (16/266, 6.0%) was about 35%. VH3-20 and VH3-49 only occurred in un-IgHV (P<0.05). In addition, the expression rates of CD38 (26.3% vs. 3.0%), CD79b (71.1%∶45.5%) and 11q deletion (25.5%∶5.3%) were higher in un-IgHV, and single trisomy 12 (37.9%∶5.6%) were more commonly found in m-IgHV (P<0.05). MYD88 was one of the major mutation genes in m-IgHV, while ATM had the highest mutation rate in un-IgHV. Conclusion: CLL patients have differential expression in terms of IgHV gene mutations, correlating to their immunophenotype and genetics characteristics.

[Characteristics of fusion gene expression in acute lymphoblastic leukemia].

Objective: To analyze the genetic landscape of 52 fusion genes in patients with de novo acute lymphoblastic leukemia (ALL) and to investigate the characteristics of other laboratory results. Methods: The fusion gene expression was retrospectively analyzed in the 1 994 patients with de novo ALL diagnosed from September 2016 to December 2020. In addition, their mutational, immunophenotypical and karyotypical profiles were investigated. Results: In the 1 994 patients with ALL, the median age was 12 years (from 15 days to 89 years). In the panel of targeted genes, 15 different types of fusion genes were detected in 884 patients (44.33%) and demonstrated a Power law distribution. The frequency of detectable fusion genes in B-cell ALL was significantly higher than that in T-cell ALL (48.48% vs 18.71%), and fusion genes were almost exclusively expressed in B-cell ALL or T-cell ALL. The number of fusion genes showed peaks at<1 year, 3-5 years and 35-44 years, respectively. More fusion genes were identified in children than in adults. MLL-FG was most frequently seen in infants and TEL-AML1 was most commonly seen in children, while BCR-ABL1 was dominant in adults. The majority of fusion gene mutations involved signaling pathway and the most frequent mutations were observed in NRAS and KRAS genes. The expression of early-stage B-cell antigens varied in B-cell ALL patients. The complex karyotypes were more common in BCR-ABL1 positive patients than others. Conclusion: The distribution of fusion genes in ALL patients differs by ages and cell lineages. It also corresponds to various gene mutations, immunophenotypes, and karyotypes.

[Clinical characteristics of high-grade B-cell lymphomas with rearrangement of MYC, bcl-6 and bcl-2].

Objective: To investigate the clinicopathologic features of patients with high-grade B-cell lymphomas (HGBL) that have rearrangements of MYC, bcl-6 and bcl-2. Methods: One hundred and fifty-eight B-cell lymphomas patients from Institute of Hematology and Blood Diseases Hospital from January 2016 to April 2017 were detected by fluorescence in situ hybridization (FISH) with double color split-apart probes. Results: Among 158 B-cell lymphomas, 3 cases with MYC, bcl-2 and bcl-6 rearrangements were identified, 1 of which also had CCND1/IgH translocation. All three patients were of older age, with poor prognostic parameters, multiple organs involvements, elevated LDH and advanced-tumor stage. Two of the three patients were treated with high-intensity chemotherapy and had no remission with an overall survival of 9 months and 11 months respectively. One patient had follow-up with no treatment. Histologically, all three cases showed a spectrum of morphologic features. Although initially categorized as lymphoblastic lymphoma, diffuse large lymphoma and mantle cell lymphoma respectively, two cases were associated with germinal center B-cell (GCB) immunophenotype and 1 case with non-GCB immunophenotype. They had a high proliferation index as assessed by immunostaining for Ki-67 (60%-90%). Conclusions: MYC(+) bcl-2(+) bcl-6(+) HGBL is an aggressive disease with multiple organ involvement, high serum LDH levels, advanced stage disease, poor prognosis and shorter patient survival. The diagnosis should be made by histopathology combined with FISH analysis. Its separation from other types of B cell large cell lymphoma is of clinical importance.

[Clinicopathologic characteristics of plasma cell myeloma with marrow fibrosis].

Objective: To study the clinicopathologic features of plasma cell myeloma(PCM) with bone marrow fibrosis (MF). Methods: The clinicopathologic data of 175 cases of newly diagnosed PCM patients were retrospectively analyzed. Based on reticular fiber staining, these cases were divided into PCM-MF and non-PCM-MF groups. Results: Sixty-three cases were PCM-MF(36%), 112 were non-PCM-MF (64%). No statistical difference in gender, age, hemoglobin level, platelet counts, the classification of immunoglobulin, ISS staging, immunohistochemical phenotypes and genetic features was found between PCM-MF and non-PCM-MF groups (P>0.05). Compared to non-PCM-MF group, lactate dehydrogenase (LDH)level and renal impairmentrate were higher in PCM-MF group (P<0.05). The degree of bone marrow hyperplasia, the percentage of myeloma cells and cells with plasmablastic morphology were significantly higher in PCM-MF group(P<0.05). Conclusion: The higher LDH level, renal impairment rate, and more significant bone marrow hyperplasia, proliferation of plasma cells and plasmablastic myeloma cells infiltration indicate poor prognosis of PCM-MF patients.

Hypochondriacal patients' appraisal of health and physical risks.

OBJECTIVE: The authors' goal was to assess the degree to which hypochondriasis is accompanied by a heightened sense of risk of disease and other physical hazards. METHOD: Fifty-six patients meeting DSM-III-R criteria for hypochondriasis were compared with 127 nonhypochondriacal patients from the same primary care setting. Both groups completed a self-report questionnaire assessing the degree to which they felt at risk of developing various medical diseases or being subject to injury from accidents or criminal assault. RESULTS: Both groups of patients exhibited an optimistic bias in that they considered themselves to be less at risk than others of their age and sex. However, the hypochondriacal group had a significantly higher total risk score than did the nonhypochondriacal group. In large part, this intergroup difference was the result of the hypochondriacal patients' perception that they were likely to develop various diseases. The hypochondriacal group did not score significantly higher than the comparison group in estimating their risk of succumbing to accidents and criminal victimization. Perceived risk was significantly associated with the self-reported tendency to amplify benign bodily sensations. CONCLUSIONS: An exaggerated appraisal of risk, jeopardy, and vulnerability to disease may be part of the cognitive distortion seen in hypochondriasis. If this is confirmed, cognitive and behavioral therapies for hypochondriasis may need to include a focus on these patients' understanding and appraisal of risk.

Ultrasensitive chemiluminescence detection of sub-fM level Co(II) in capillary electrophoresis.

A method of on-line ultrasensitive chemiluminescence detection with capillary electrophoresis for Co(II) is reported. Using our newly developed capillary electrophoresis with chemiluminescence detection system and novel mixing mode of the reagents, the effects of field-amplified injection on detection limits of metal ions were studied in detail. The sub-fM level (1.3 x 10(-16) M, 1.6 x 10(-24) mol, 1 molecule) detection of cobalt ions in ultradilute solution was performed. The catalytic behavior of the chemiluminescence reaction of luminol and hydrogen peroxide by cobalt ions and the reaction conditions, such as the concentration of luminol, H2O2, and pH of chemiluminescence reagent were investigated. The separation of fM level Co(II) and trace amounts of Ni(II) was performed successfully.