Background: Chronic lymphocytic leukemia (CLL) results in increased susceptibility to infections. T cell dysfunction is not associated with CLL in all patients; therefore, it is important to identify CLL patients with T cell defects. The role of B-cell lymphoma-2 (BCL-2) in CLL has been explored; however, few studies have examined its role in T cells in CLL patients. Herein, we have investigated the regulatory role of BCL-2 in T cells in the CLL tumor microenvironment.Methods: The expression of BCL-2 in T cells was evaluated using flow cytometry. The regulatory roles of BCL-2 were investigated using single-cell RNA sequencing (scRNA-seq) and verified using multi-parameter flow cytometry on CD4 and CD8 T cells. The clinical features of BCL-2 expression in T cells in CLL were also explored.Results: We found a significant increase in BCL-2 expression in the T cells of CLL patients (n = 266). Single cell RNA sequencing (scRNA-seq) indicated that BCL-2⁺CD4⁺T cells had the gene signature of increased regulatory T cells (Treg); BCL-2⁺CD8⁺T cells showed the gene signature of exhausted cytotoxic T lymphocytes (CTL); and increased expression of BCL-2 was associated with T cell activation and cellular adhesion. The results from scRNA-seq were verified in peripheral T cells from 70 patients with CLL, wherein BCL-2⁺CD4⁺T cells were enriched with Tregs and had higher expression of interleukin-10 and transforming growth factor-β than BCL-2⁻CD4⁺T cells. BCL-2 expression in CD8⁺T cells was associated with exhausted cells (PD-1⁺Tim-3⁺) and weak expression of granzyme B and perforin. T cell–associated cytokine profiling revealed a negative association between BCL-2⁺T cells and T cell activation. Decreased frequencies and recovery functions of BCL-2⁺T cells were observed in CLL patients in complete remission after treatment with venetoclax.Conclusion: BCL-2 expression in the T cells of CLL patients is associated with immunosuppression via promotion of Treg abundance and CTL exhaustion.

T-cell large granular lymphocytic leukemia (T-LGLL) is a rare lymphoproliferative disorder and can cooccur in the context of pure red cell aplasia (PRCA). The aim of the current study was to analyze the signal transducer and activator of transcription 3 (STAT3) mutation status and its clinical significance in T-LGLL. We found STAT3 mutations in 21.4% of patients with T-LGLL. High β2-MG (β2-microglobulin) levels (P = 0.005), neutropenia (P = 0.018) and PRCA (P = 0.001) all displayed a significant association with STAT3 mutations. In univariate analysis, treatment-free survival (TFS) was affected by STAT3 mutation status (P = 0.008) and β2-MG (P = 0.006). Our results demonstrate the remarkable correlation of STAT3 mutation with PRCA, neutropenia and β2-MG.

Multiple myeloma (MM) involves a clinically and biologically heterogeneous malignancy of plasma cells. It is difficult to predict the prognosis of MM. The presence of circulating clonal plasma cell...

The incidence of B‐cell chronic lymphoproliferative disorders (B‐CLPDs) is significantly lower in China than that in western countries. There have been studies involving small cohorts with conflicting results regarding the spectrum of B‐CLPDs in China, and the types and immunophenotyping of B‐CLPDs in China remain largely unexplored. We conducted a retrospective analysis of 653 cases of B‐CLPDs seen in our centre from 2011 to 2015. Four‐colour flow cytometry was used to determine the expression of each immunological marker, and the diagnostic values of the immunological markers were also investigated. Chronic lymphocytic leukaemia (CLL) was the most common type of B‐CLPD, which was consistent with that in west countries. However, the proportions of CLL (55.9%), follicular lymphoma (2.6%), and hairy cell leukaemia (0.2%) were lower, while the proportion of lymphoplasmacytic lymphoma/WaldenstrÖm macroglobulinaemia (5.4%) was higher in China, as compared with western countries. With respect to immunophenotypic characteristics, CD23 (31.7%) was more frequently expressed in mantle cell lymphoma (MCL) in our cohort than that in western countries. Immunophenotyping was useful in differentiating MCL from CLL or B‐cell prolymphocytic leukaemia and lymphoplasmacytic lymphoma/WaldenstrÖm macroglobulinaemia from splenic marginal zone lymphoma. CD200 was of better diagnostic performance (accuracy: 94.6%) in differentiating CLL from MCL compared with CD23 (accuracy: 93.3%). Some cases of B‐CPLDs, however, had no definite diagnoses, which were diagnosed as CD5⁺B‐CPLDs unclassified (7.7%) and CD5⁻B‐CPLDs unclassified (15.8%). This is the largest study that systematically explores the spectrum and immunophenotyping of B‐CLPDs in Asia, confirming that spectrum of B‐CLPDs in China was different from that in western countries. The immunophenotypic features of B‐CLPDs were similar between China and western countries, although a few disparities exist. Cases with no definite diagnoses warrant further studies in the future.

The study aims to understand geneome diversification and complexity that developed in Acute myeloid leukemia (AML).Next-generation sequencing (NGS) was used to identify the genetic profiles of 22 gen...

Rapid and accurate detection of BCR-ABL fusion proteins is vital for the diagnosis and classification of leukemias, especially chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). Recently, the cytometric bead array (CBA) system has been used to identify BCR-ABL proteins in leukemic cell lysates. To evaluate the accuracy of this new technique, we tested 70 patients with hematological diseases using the CBA system, cytogenetic analysis, fluorescence in situ hybridization (FISH) and real-time quantitative polymerase chain reaction (RQ-PCR). Most of the results obtained by the CBA system were concordant with those by cytogenetic analysis, FISH and RQ-PCR. In the CBA system, dilution experiments with positive control samples revealed sensitivities of at least 1%. The statistical analysis revealed that the mean fluorescence intensity (MFI) values of the BCR-ABL fusion proteins from mononuclear cells (MNCs) were higher than those from WBC or BM samples. The MFI values of cells were not dramatically reduced after 24 hours of storage at room temperature. The CBA technique detected all types of BCR-ABL proteins in leukemic cells with high specificity and sensitivity. Therefore, CBAs will contribute to the fast and easy diagnosis of leukemias, the classification of leukemias and the monitoring of minimal residual disease (MRD).