Effective treatment with Gilteritinib-based regimens for FLT3-mutant extramedullary relapse in acute promyelocytic leukemia.

OBJECTIVE: Extramedullary relapse (EMR) is rare in acute promyelocytic leukemia (APL) and, there is a lack of information on its management. Current practices for EMR in APL are always to adopt strategies from other subtypes of Acute lymphoblastic leukemia (ALL) and Acute myeloid leukemia (AML). Gilteritinib, a highly selective FLT3 inhibitor, has demonstrated a remarkable effect on EMR in FLT3-mutant AML. Therefore, it is worthwhile exploring if FLT3 mutation can be a therapeutic target and assessing the efficacy of Gilteritinib on FLT3-mutant EMR in APL. METHODS: We described three cases of FLT3-mutant EMR in APL, comprising two isolated EMR cases and one systemic relapse. The patients underwent treatment with Gilteritinib-based regimens based on FLT3 mutation. RESULTS: All three patients achieved complete regression of EMR, and no signs of tumor lysis syndrome during Gilteritinib-based therapy, only patient 1 showed mild granulocytopenia. They all maintained molecular complete remission (mCR) during the follow-up period. CONCLUSIONS: The Gilteritinib-based regimen shows a high and sustained therapeutic effect with minimal adverse effects, and provides a valuable experience for further evaluation in EMR APL patients.

Identification of two transcription factors activating the expression of OsXIP in rice defence response.

BACKGROUND: Xylanase inhibitors have been confirmed to be involved in plant defence. OsXIP is a XIP-type rice xylanase inhibitor, yet its transcriptional regulation remains unknown. RESULTS: Herbivore infestation, wounding and methyl jasmonate (MeJA) treatment enhanced mRNA levels and protein levels of OsXIP. By analyzing different 5' deletion mutants of OsXIP promoter exposed to rice brown planthopper Nilaparvata lugens stress, a 562 bp region (-1451 - -889) was finally identified as the key sequence for the herbivores stress response. Using yeast one-hybrid screening, coupled with chromatin immunoprecipitation analysis, a basic helix-loop-helix protein (OsbHLH59) and an APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factor OsERF71 directly binding to the 562 bp key sequence to activate the expression of OsXIP were identified, which is further supported by transient expression assay. Moreover, transcriptional analysis revealed that mechanical wounding and treatment with MeJA resulted in an obvious increase in transcript levels of OsbHLH59 and OsERF71 in root and shoot tissues. CONCLUSIONS: Our data shows that two proteins as direct transcriptional activators of OsXIP responding to stress were identified. These results reveal a coordinated regulatory mechanism of OsXIP, which may probably be involved in defence responses via a JA-mediated signaling pathway.

Effects of an exogenous xylanase gene expression on the growth of transgenic rice and the expression level of endogenous xylanase inhibitor gene RIXI.

BACKGROUND: Xylanases have attracted considerable interest in recent years owing to their various applications in industry and agriculture. The use of transgenic plants to produce xylanases is a less expensive alternative to biotechnological programmes. The aim of this study was to elucidate whether introducing a foreign xylanase gene ATX into rice had any adverse effect on plant growth and development. RESULTS: A recombinant xylanase gene ATX was introduced into rice variety Zhonghua 11 through Agrobacterium-mediated transformation. The T2 generation of transgenic rice was compared with the control (non-transgenic plants). Exogenous xylanase gene ATX was expressed in rice, and all examined transgenic lines exhibited xylanase activity. The transgenic lines (T2, 'X1-3' and 'X2-5') appeared to grow and develop normally. There were no differences in net photosynthetic rate between transgenic rice lines ('X1-3' and 'X2-5') and wild type (WT) rice plants at the heading/flowering stage. Xylanases are key enzymes in the degradation of plant cell walls. Cell wall composition analysis showed that that there were no changes in cell wall polysaccharides in the root apex but some alterations in leaves in transgenic rice plants. The results also showed that the expression of exogenous xylanase gene ATX in rice would increase the expression of endogenous xylanase inhibitor gene RIXI, which could play a role in plant defence. Thus the stress resistance of transgenic rice plants might be improved. CONCLUSION: Exogenous xylanase gene ATX could be successfully expressed in rice, and the exogenous protein had no apparent harmful effects on growth and development in transgenic rice plants.