Olverembatinib combined with blinatumomab in treating T315I-mutated Philadelphia chromosome-positive acute lymphoblastic leukemia: two-case report.

ABL tyrosine kinase inhibitors (TKIs) act an irreplaceable role in the management of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). The treatment of these diseases has been revolutionized by the application of immunotherapeutic modalities. However, diseases with ABL kinase domain mutation T315I are resistant to the majority of TKIs, which is responsible for treatment failure. Olverembatinib is a third-generation TKI that has been approved for the treatment of T315I-mutated chronic myeloid leukemia (CML) in China; its usage in Ph+ ALL needs further exploration. Here, we present two cases with relapsed T315I mutation Ph+ ALL who received the combination regimen of blinatumomab and olverembatinib. This regimen, which has not been reported yet, was safe and effective as the patients achieved minimal residual disease (MRD) negative after 1 cycle of therapy. The management of these cases provides evidence of this new chemo-free regimen as an efficient approach for relapsed or refractory(R/R)Ph+ ALL.

Identification of mast cells as a candidate significant target of immunotherapy for acute myeloid leukemia.

OBJECTION: Immunotherapy based on T cells is a new therapy for Acute myeloid leukemia (AML). However, there has not been considerable improvement compared with traditional chemotherapeutics. This study aimed to identify important immune cells, genes, and drugs associated with the immunotherapy of AML. METHODS: The gene expression profile and clinical data of patients with AML were downloaded from TCGA database, and the abundance ratio of immune cells was obtained via CIBERSORT. Kaplan-Meier (KM) survival analysis was used to assess the relationship between immune cells and survival time of patients with AML. Differentially expressed genes (DEGs) analysis was conducted to obtained DEGs related to mast cells. Then, protein-protein interaction (PPI) analysis and enrichment analysis were performed to explore the hub genes. Finally, Connectivity Map (CMap) database was utilized to predicts potential drugs that may reverse or induce the mast cell-related gene expression. RESULTS: Our study showed that mast cell was correlated with survival time of patients with AML, and 135 genes were screened to be related with mast cells. 6 hub genes were identified via PPI network, and 3 potential small molecule drugs were screened to be related to regulating the mast cell-related gene expression via CMap database. CONCLUSION: The hub genes and drugs have high research value and clinical application in AML therapy. Our study not only provides gene targets and small molecule drugs for AML immunotherapy concerning mast cells but also provides new ideas for researchers to explore immunotherapy targets of other tumors.