Search

Background This study aims to explore the mechanism of drug resistance in multiple myeloma (MM). Methods In this study, the possible mechanism of chemotherapeutic tolerance was preliminarily explored from two aspects: (I) the changes in cell morphology, cell cycle, cell apoptosis, stem cell markers and the signaling transduction pathway after the irradiation of RPMI-8226 cells; (II) the mechanism of enhancing chemotherapeutic sensitivity through the PI3K/AKT/mTOR signaling pathway. Results The results showed that the cell morphology and cell cycle of RPMI-8226 had been significantly changed after receiving a radiation dose of 6 Gy in the logarithmic growth phase, the sensitivity of cells to bortezomib had been decreased, the level of stem cell markers had been upregulated, and the PI3K/AKT/mTOR signaling pathway had been activated. However, blocking the PI3K/AKT/mTOR signaling pathway caused the expression of the stem cell markers of RPMI-8226 cells. In addition, the sensitivity of cells to bortezomib had been increased. Conclusions Blocking the PI3K/AKT/mTOR might decrease the RPMI-8226 cells which survived the radiotherapy and increase the sensitivity of cells to bortezomib.

Additional file 1: Supplementary 1.GEBoxplot of individual systemic exposure of selinexor in Chinese and western populations. ATG-010-MM-001: NCT03944057; KCP-330-001 [15, 17, 19]: NCT01607892; KCP-330-002 [16]: NCT01607905; KCP-330-003 [18]: NCT01896505.

Introduction Philadelphia chromosome (Ph) is a hallmark of chronic myeloid leukemia (CML), which exists in more than 90% CML and in 3% to 40% acute lymphoblastic leukemia (ALL). Case description A 25-year-old man was diagnosed with CML in chronic phase. He first received treatment with hydroxyurea, achieving hematological remission and following imatinib mesylate for main treatment. A year later, he began to appear unexplained high fever with ineffective antibiotic treatment and bone morrow and blood tests indicated blast crisis. Both BCR/ABL 210 and BCR/ABL 190 fusion transcript were positive. Imatinib resistance was confirmed by a screening for ABL kinase domain E255K mutations, and dasatinib was administered. After two months, the patient went on to hematological remission. Discussion and evaluation During medical treatment for CML, we experienced a relatively rare case with co-expression of the p210 and p190 encoding BCR-ABL transcripts in blastic phase. Imatinib resistance was confirmed and remission wasn’t easily obtained, yet dasatinib was helpful. When resistance emerges, the treatment options include increasing the daily dose of imatinib, or combining imatinib with other agents. Of course, dasatinib, nilotinib and bone marrow transplantation are good choice as well. Conclusions The presence of p-190 transcript in CML may be related to progression of the disease. Thus monitoring the resistance of imatinib in CML patients, especially for advanced phase CML and BCR-ABL ALL, may be meaningful to guide clinical treatment and predict the prognosis.