Objective:To investigate the relationship between the BCL2 family protein BIM and ibrutinib resistance in chronic lymphocytic leukemia (CLL) and to analyze its regulatory mechanisms on apoptosis and autophagy.Methods:RNA sequencing (RNA-seq) was used to examine changes in the expression of BCL2 family proteins in samples from patients with CLL, MEC1 cell lines, and ibrutinib-resistant cell lines (MR). Western blot was used to analyze changes in BIM protein expression during apoptosis in MR. shRNA knockdown was used to assess the effects of BIM on cell proliferation and apoptosis. RNA-seq and the autophagy inhibitor chloroquine treatment were used to study autophagy-related changes in MR.Results:BIM expression was significantly downregulated before and after drug resistance in CLL primary cells and MEC1 cell lines ( P<0.0001). Knockdown of BIM in CLL cells inhibited ibrutinib-induced apoptosis and promoted cell proliferation ( P<0.05 for both). In addition, protective autophagy was increased in MR and apoptosis was increased after administration of chloroquine and small interfering RNA. The increased expression of LC3-Ⅱ protein in BIM-knockdown cell lines ( P<0.01) suggested that reduction of BIM may mediate autophagy activation. Conclusion:Downregulation of BIM may be a key factor in promoting ibrutinib resistance in CLL by activating protective autophagy. These findings provided a potential target for improving CLL treatment.

Objective:To investigate the relationship between the BCL2 family protein BIM and ibrutinib resistance in chronic lymphocytic leukemia (CLL) and to analyze its regulatory mechanisms on apoptosis and autophagy.Methods:RNA sequencing (RNA-seq) was used to examine changes in the expression of BCL2 family proteins in samples from patients with CLL, MEC1 cell lines, and ibrutinib-resistant cell lines (MR). Western blot was used to analyze changes in BIM protein expression during apoptosis in MR. shRNA knockdown was used to assess the effects of BIM on cell proliferation and apoptosis. RNA-seq and the autophagy inhibitor chloroquine treatment were used to study autophagy-related changes in MR.Results:BIM expression was significantly downregulated before and after drug resistance in CLL primary cells and MEC1 cell lines ( P<0.0001). Knockdown of BIM in CLL cells inhibited ibrutinib-induced apoptosis and promoted cell proliferation ( P<0.05 for both). In addition, protective autophagy was increased in MR and apoptosis was increased after administration of chloroquine and small interfering RNA. The increased expression of LC3-Ⅱ protein in BIM-knockdown cell lines ( P<0.01) suggested that reduction of BIM may mediate autophagy activation. Conclusion:Downregulation of BIM may be a key factor in promoting ibrutinib resistance in CLL by activating protective autophagy. These findings provided a potential target for improving CLL treatment.

Objective:This study aimed to assess the efficacy and safety of thioamide as a maintenance therapy for peripheral T-cell lymphoma (PTCL) .Methods:This study retrospectively analyzed the data from 58 patients with PTCL who were treated in the Department of Hematology at the First Affiliated Hospital of Nanjing Medical University from January 2015 to July 2022. Chidamide was orally administered as a maintenance therapy after first-line or salvage treatment. Progression-free survival (PFS), overall survival (OS), and safety were analyzed.Results:Among the 58 patients with PTCL, 43 were males and 15 were females, and the median age was 66 (range: 29-83) years. Thirty-nine patients received thioamide as first-line maintenance therapy, and 19 patients received thioamide as maintenance therapy after salvage treatment. The median maintenance therapy duration was 16 months (range: 1-72 months), with a median PFS time of 33 (2-74) months, and the median OS time had not been reached. Patients who received first-line maintenance therapy with thioamide demonstrated superior PFS and OS outcomes compared with patients who received thioamide maintenance therapy after salvage treatment (median PFS time: not reached vs 7 months, P<0.001; median OS time: not reached vs 67 months, P=0.009). The most prevalent adverse reaction was a hematologic adverse reaction (77.6%). Twelve (20.7%) patients underwent a dose reduction and three patients discontinued treatment. Conclusion:Patients receiving thioamide maintenance therapy demonstrated a promising PFS and OS with a manageable safety profile, especially as the first-line maintenance therapy.

Objective:This study aimed to assess the efficacy and safety of thioamide as a maintenance therapy for peripheral T-cell lymphoma (PTCL) .Methods:This study retrospectively analyzed the data from 58 patients with PTCL who were treated in the Department of Hematology at the First Affiliated Hospital of Nanjing Medical University from January 2015 to July 2022. Chidamide was orally administered as a maintenance therapy after first-line or salvage treatment. Progression-free survival (PFS), overall survival (OS), and safety were analyzed.Results:Among the 58 patients with PTCL, 43 were males and 15 were females, and the median age was 66 (range: 29-83) years. Thirty-nine patients received thioamide as first-line maintenance therapy, and 19 patients received thioamide as maintenance therapy after salvage treatment. The median maintenance therapy duration was 16 months (range: 1-72 months), with a median PFS time of 33 (2-74) months, and the median OS time had not been reached. Patients who received first-line maintenance therapy with thioamide demonstrated superior PFS and OS outcomes compared with patients who received thioamide maintenance therapy after salvage treatment (median PFS time: not reached vs 7 months, P<0.001; median OS time: not reached vs 67 months, P=0.009). The most prevalent adverse reaction was a hematologic adverse reaction (77.6%). Twelve (20.7%) patients underwent a dose reduction and three patients discontinued treatment. Conclusion:Patients receiving thioamide maintenance therapy demonstrated a promising PFS and OS with a manageable safety profile, especially as the first-line maintenance therapy.

Hodgkin lymphoma (HL) is a highly curable malignancy for most patients, while the treatment of relapsed and refractory HL is still a difficult and important field. A high dose of chemotherapy with autologous stem cell transplantation is treated as the preferred treatment with a high relapse incidence. The 59th American Society of Hematology Annual Meeting reported the recent progress of the treatment of relapsed and refractory HL, including the improvement of traditional high dose chemotherapy regimens, the new drugs or therapies like brentuximab vedotin, nivolumab, pembrolizumab and ibrutinib, and chimeric antigen receptor T-cell. This review focuses on these advances.