AXL belongs to the TAM (TYRO3, AXL, and MERTK) receptor family, a unique subfamily of the receptor tyrosine kinases. Their common ligand is growth arrest-specific protein 6 (GAS6). The GAS6/TAM signaling pathway regulates many important cell processes and plays an essential role in immunity, hemostasis, and erythropoiesis. In cancer, AXL overexpression and activation has been associated with cell proliferation, chemotherapy resistance, tumor angiogenesis, invasion, and metastasis; and has been correlated with a poor prognosis. In hematological malignancies, the expression and function of AXL is highly diverse, not only between the different tumor types but also in the surrounding tumor microenvironment. Most research and clinical evidence has been provided for AXL inhibitors in acute myeloid leukemia. However, recent studies also revealed an important role of AXL in lymphoid leukemia, lymphoma, and multiple myeloma. In this review, we summarize the basic functions of AXL in various cell types and the role of AXL in different hematological cancers, with a focus on AXL in the dormancy of multiple myeloma. In addition, we provide an update on the most promising AXL inhibitors currently in preclinical/clinical evaluation and discuss future perspectives in this emerging field.

Exosomes were reported to mediate cell communication in the tumor microenvironment; however, the effects of multiple myeloma (MM)-derived exosomes on the quantity and function of T cells remain unknown. Exosomes were extracted from MM cell lines (OPM2 and U266B1) by ultracentrifugation using a Total Exosome Isolation kit. Exosomes were co-cultured with CD4+ T, CD8+ T and regulatory T (Treg) cells that were isolated from healthy donors (HDs) and patients with MM using magnetic beads. Flow cytometry was used to detect T cells apoptosis and expression of perforin and granzyme B in CD8+ T cells. Cell viability was detected using Cell Counting kit-8, and interleukin 10 (IL-10) and transforming growth factor β (TGF-β) in cell supernatants were detected by ELISA. The apoptosis of HD-CD4+ T was higher in the OPM2 group, and viability in the U266B1 group was decreased. The apoptosis of HD-CD8+ T decreased in the OPM2 and U266B1 groups, and cell viability increased in the OPM2 and the U266B1 groups. Perforin of HD-CD8+ T in the U266B1 group was lower while perforin of MM-CD8+ T in OPM2 and U266B1 groups was markedly decreased. The apoptosis of HD-Treg was lower in the U266B1 group, but apoptosis of MM-Treg was higher in the U266B1 group. The viability of HD-Treg in U266B1 group increased but the viability of MM-Treg in OPM2 and U266B1 groups decreased. TGF-β from MM-Treg decreased in the OPM2 and U266B1 groups when compared with the control group (P<0.05). MM-derived exosomes promote apoptosis and inhibit proliferation of HD-CD4+ T, inhibit apoptosis and promote proliferation, but inhibit perforin of HD-CD8+ T, inhibit apoptosis and promote proliferation HD-Treg, and inhibit perforin of MM-CD8+ T and TGF-β secretion of MM-Treg.

This retrospective study aims at confirming the efficacy and safety of low dose rituximab and pulse cyclophosphamide in the treatment of refractory AIHA in adults and making comparison of the two. Forty-nine adult patients with refractory AIHA have been enrolled. Results showed low dose rituximab combined with steroid therapy (group B) got more CR (78.9 %, 15/19) compared to that in intermittent intravenous cyclophosphamide combined with steroid therapy (group A) (42.1 %, 8/19) (P = 0.04) at 6 months after treatment. The hemoglobin level in group B was higher than group A at the time point of 1 month (P = 0.02) after treatments. The RFS in group A was 87.9 % at 6 months and 82.7 % at 12 months, which were no significant difference with group B (91.1 % at 6 months and 86.0 % at 12 months) (P = 0.81). Both the two therapies were well tolerated with pulmonary infections as the most common side effects. In conclusion, low dose rituximab combined with steroid therapy presents to be a better choice in the treatment of refractory AIHA in adults comparing with pulse cyclophosphamide therapy.

Selectively anchoring active centers on the external surface for forming highly exposed acid sites is a highly desirable but challenging task in zeolite catalyst synthesis. Herein, a defect-guided etching-regrowth strategy is rationally designed for facilely positioning Sn Lewis acid sites on the outer surface of the Sn-B-Beta while fabricating a bifunctional hierarchical structure. The synthesis was conducted by hydrothermal treatment of the as-made B-Beta (uncalcined), which has intrinsic defects of the BEA structure, with Sn source and basic organic structure directing agent (SDA). Under a moderate SDA concentration, with blocked micropore channels, such SDA-triggered etching-regrowth will proceed along the defect defined pathway, which ensures Sn selectively anchored on the external surface. Moreover, this methodology has exclusively introduced tetrahedrally coordinated framework Sn with open Sn sites as the predominated species. Mono- and disaccharide isomerizations in ethanol over different Sn-Beta catalysts proved the prominent advantages of the hierarchical structure with highly exposed and synergetic acid sites.