Chimeric antigen receptor (CAR) T-cell immunotherapy following autologous stem cell transplantation (ASCT) is a promising method for refractory or relapsed multiple myeloma, but explicit data for central nervous system lymphoma (CNSL) are lacking. Here, we treated 13 CNSL patients with ASCT sequential CD19/22 CAR T-cell infusion and simultaneously evaluated the clinical efficacy and toxicity. The 13 CNSL patients analyzed included four primary CNSL and nine secondary CNSL patients. Patients 1 and 10, who had complete remission status before enrollment, maintained clinical efficacy without recurrence. Nine of the remaining 11 patients responded to our protocol with a median durable time of 14.03 months, and the overall response and complete remission rate were 81.81% and 54.55%, respectively. No patient suffered grades 3–4 cytokine-release syndrome (CRS), and only patient 10 experienced severe immune effector cell-associated neurotoxicity syndrome (ICANS). In addition, increases in serum ferritin and interleukin-6 levels were often accompanied by CRS and ICANS. After a median follow-up time of 14.20 months, the estimated 1-year progression-free survival and overall survival rates were 74.59% and 82.50%, respectively. Sequential CD19/22 CAR T-cell immunotherapy following ASCT as a novel method for CNSL appears to have encouraging long-term efficacy with relatively manageable side effects.

Circular RNAs are relevant to progression of acute myeloid leukemia (AML). Nevertheless, how and whether hsa_circ_0002483 (circ_0002483) participates in AML progression are largely uncertain. The bone marrow samples were harvested from 31 AML patients or 31 normal subjects. Circ_0002483, microRNA (miR)‐758‐3p and myelocytomatosis oncogene (MYC) abundances were examined via quantitative reverse transcription polymerase chain reaction and Western blot. Cell proliferation, cycle process and apoptosis were analyzed via Cell Counting Kit‐8, flow cytometry, caspase 3 activity and related protein levels. Target relationship was investigated by dual‐luciferase reporter assay and RNA immunoprecipitation. Circ_0002483 expression was elevated in AML patients and cells. Circ_0002483 silence constrained AML cell proliferation and facilitated cell cycle arrest and apoptosis. miR‐758‐3p was reduced in AML and decreased via circ_0002483. miR‐758‐3p down‐regulation mitigated the inhibitive influence of circ_0002483 interference on AML progression. MYC was decreased by miR‐758‐3p, and circ_0002483 could regulate MYC expression by miR‐758‐3p. miR‐758‐3p overexpression restrained cell proliferation and promoted cycle arrest and apoptosis via decreasing MYC. Circ_0002483 knockdown repressed AML cell proliferation and promoted cycle arrest and apoptosis via controlling miR‐758‐3p/MYC axis.

Acute myeloid leukemia (AML) is a highly heterogeneous disease featured by a clonal proliferation derived from primitive hematopoietic stem/progenitor cells. Circular RNAs (circRNAs) have been identified as crucial regulators in the progression of various cancers, including AML. However, the molecular mechanism of AML is still not definite. This study aimed to explore the influences of circ_0012152 on cell development in AML cells and the underlying regulatory mechanism. The expression of circ_0012152, microRNA‐625‐5p (miR‐625‐5p) and sex‐determining region Y‐related high mobility group box 12 (SOX12) was detected by quantitative real‐time polymerase chain reaction. The proliferation of AML cells was evaluated by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay for cell viability, 5‐ethynyl‐2′‐deoxyuridine incorporation assay for DNA biosynthesis and flow cytometry for cell cycle distribution, respectively. The death of AML cells was detected by flow cytometry. The protein expression was assessed by Western blot assay. Dual‐luciferase reporter and RNA immunoprecipitation assays were carried out to examine the relationships among circ_0012152, miR‐625‐5p and SOX12. The expression of circ_0012152 was increased in AML tissues and cells and circ_0012152 knockdown suppressed proliferation and promoted death in AML cells. Further exploration revealed that circ_0012152 inhibited miR‐625‐5p expression and downregulation of miR‐625‐5p overturned the effects of circ_0012152 knockdown on proliferation and death in AML cells. Moreover, miR‐625‐5p targeted SOX12 and circ_0012152 facilitated the expression of SOX12 by relieving miR‐625‐5p‐mediated inhibitory effect on SOX12 in AML cells. Circ_0012152 knockdown suppressed cell proliferation and promoted death by targeting SOX12 mediated by miR‐625‐5p in AML cells.