Transformation of marginal zone lymphoma into high-grade B-cell lymphoma expressing terminal deoxynucleotidyl transferase: A case report.

BACKGROUND: High-grade B-cell lymphoma (HGBL) is an unusual malignancy that includes myelocytomatosis viral oncogene (MYC), B-cell lymphoma-2 (BCL-2), and/or BCL-6 rearrangements, termed double-hit or triple-hit lymphomas, and HGBL-not otherwise specific (HGBL-NOS), which are morphologically characteristic of HGBL but lack MYC, BCL-2, or BCL-6 rearrangements. HGBL is partially transformed by follicular lymphoma and other indolent lymphoma, with few cases of marginal zone lymphoma (MZL) transformation. HGBL often has a poor prognosis and intensive therapy is currently mainly advocated, but there is no good treatment for these patients who cannot tolerate chemotherapy. CASE SUMMARY: We reported a case of MZL transformed into HGBL-NOS with TP53 mutation and terminal deoxynucleotidyl transferase expression. Gene analysis revealed the gene expression profile was identical in the pre- and post-transformed tissues, suggesting that the two diseases are homologous, not secondary tumors. The chemotherapy was ineffective and the side effect was severe, so we tried combination therapy including venetoclax and obinutuzumab. The patient tolerated treatment well, and reached partial response. The patient had recurrence of hepatocellular carcinoma and died of multifunctional organ failure. He survived for 12 months after diagnosis. CONCLUSION: Venetoclax combined with obinutuzumab might improve the survival in some HGBL patients, who are unsuitable for chemotherapy.

Myeloproliferative neoplasms complicated with ß-thalassemia: Two case report.

BACKGROUND: BCR-ABL-negative myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the proliferation of one or more myeloid lineages and by mutually exclusive JAK2 V617F, CALR, and MPL[A1] mutations. The combination of MPN and thalassemia is extremely unusual. Several cases with myeloproliferative neoplasms and ß-thalassemia have been reported. However, these have not been extensively reviewed. The present report describes two cases of myeloproliferative neoplasms complicated with ß-thalassemia and reviews all similar cases reported in the literature. CASE SUMMARY: We report two patients who were diagnosed with myeloproliferative neoplasms complicated with ß-thalassemia. Both patients had abnormal increases in platelet counts. Based on bone marrow pathology and molecular biology assessment, we made the diagnosis of myeloproliferative neoplasms complicated with ß-thalassemia. The female patient was given hydroxyurea and interferon, which enabled good control of her blood counts; the male patient was given ruxolitinib tablets, thalidomide tablets, and interferon to control the condition, but the patient poorly responded to drug treatment and died of gastrointestinal bleeding six months later. CONCLUSION: Given the findings of our cases and the literature review, we hypothesize that myeloproliferative neoplasms complicated with ß-thalassemia can lead to rapid disease progression and a poor prognosis.

Refractory lymphoma treated with chimeric antigen receptor T cells combined with programmed cell death-1 inhibitor: A case report.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a common aggressive non-Hodgkin's lymphoma (NHL), accounting for 30%-40% of adult NHL. Primary testicular (PT) lymphoma is an uncommon extranodal disease representing approximately 1%-2% of lymphoma. Approximately 30%-40% of patients are refractory to frontline therapy or relapse after complete remission. Refractory DLBCL responds poorly to other lines of chemotherapy, and experiences short-term survival. CASE SUMMARY: We present a 41-year-old male patient who was diagnosed with PT-DLBCL. Further disease progression was observed after multiline chemotherapy. Chimeric antigen receptor T cells (CAR-T) therapy salvaged the patient. Unfortunately, a new mass was observed in the right adrenal area after six months. The patient was administered programmed cell death protein-1 (PD-1) inhibitor therapy and maintained progression-free survival at more than 17 mo of follow-up. CONCLUSION: Our findings support the potential benefit of CAR-T combined with PD-1 inhibitor therapies in this type of relapsed and refractory PT-DLBCL.

Inhibition of JAK2/STAT3 Signaling Pathway Suppresses Proliferation of Burkitt's Lymphoma Raji Cells via Cell Cycle Progression, Apoptosis, and Oxidative Stress by Modulating HSP70.

BACKGROUND The aim of this study was to investigate the effect of the JAK2/STAT3 pathway on the proliferation, cell cycle distribution, apoptosis, and oxidative stress of Raji cells via regulating HSP70 expression. MATERIAL AND METHODS Raji cells were divided into Blank, HSP70 siRNA, NC siRNA, AG490 (a JAK2/STAT3 signaling pathway inhibitor), and HSP70 siRNA + rh JAK2 (recombinant human JAK2) groups. HSP70 expression was detected by quantitative real-time reverse transcription-PCR (qRT-PCR); the expression levels of HSP70 and JAK2/STAT3 pathway-related proteins were evaluated by Western blotting; cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays; cell cycle distribution was observed by flow cytometry; cell apoptosis was tested by Annexin V-FITC/PI and Hoechst 33342/PI staining; reactive oxygen species (ROS) production was measured by dichloro-dihydro-fluorescein diacetate (DCFH-DA) assays; and MDA content and SOD and GSH-Px activities were determined using detection kits. RESULTS AG490 obviously down-regulated HSP70 expression, inhibited proliferation, induced cell cycle arrest at the G0/G1 phase, and promoted apoptosis in Raji cells; these effects were similar to the effects of HSP70 siRNA. Furthermore, ROS production and MDA content were increased in Raji cells treated with HSP70 siRNA or AG490, while SOD and GSH-Px activities were reduced. Raji cells in the HSP70 siRNA + rh JAK2 group did not significantly differ from those in the Blank group in regards to proliferation, cell cycle, apoptosis, and oxidative stress. CONCLUSIONS Blocking the JAK2/STAT3 signaling pathway may inhibit proliferation, induce cell cycle arrest, and promote oxidative stress and apoptosis in Raji cells via the down-regulation of HSP70.

Effects of Danshen Injection () on inhibiting proliferation and inducing apoptosis through down-regulation of mutant JAK2 gene and its protein phosphorylation in human erythroid leukemic cells.

OBJECTIVE: To explore the effects of Danshen Injection () on inhibition proliferation, inducing apoptosis and its possible mechanisms on human erythroid leukemic (HEL) cells. METHODS: The commercial Chinese patent medicine of Danshen Injection was extracted and isolated from Chinese herb of Salvia miltiorrhiza bung. The inhibition effects of proliferation were assayed by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method in HEL cells treated by Danshen Injection at various concentrations for 48 h. The cellular apoptosis was observed in morphology, analyzed by flow cytometry with annexin V and propidium iodide (PI) staining, and examined by DNA degradation ladder on agarose gel electrophoresis. Meanwhile, the expression levels of mutant Janus kinasez (JAK2) gene and phosphorylation-JAK2 (P-JAK2) protein were detected by allele specific-polymerase chain reaction and Western blot. RESULTS: The proliferation of HEL cells was effectively inhibited by Danshen Injection in a dose-dependent manner, with suppression rates from 19.46±2.31% to 50.20±5.21%. Typical apoptosis cells was observed in Danshen Injection treated HEL cells, the rates of annexin V positive cells increased obviously in a dose-dependent manner, as well as the DNA degradation ladder of apoptosis revealed on gel electrophoresis. The expression levels of mutant JAK2 gene and P-JAK2 protein reduced gradually with increasing dosage of Danshen injection. CONCLUSION: Danshen Injection could not only significantly inhibit the proliferation, but also induce apoptosis in HEL cells; down-regulation of the mutant JAK2 gene and P-JAK2 protein expressions are probably one of its molecular mechanisms.