The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

To detect the effect of nitric oxide (NO)on basal and reflex release of oxytocin (OT),L-arginine(the substrate of NO synthase )and NG-nitro-L-arginine methyl ester (L-NAME,NO synthase inhibitor)were intracerebroventricularly(icv)administrated into the pentobarbital anesthetized rats and the plasma OT level was detected with radioimmunoassay.Injection (icv) of L-arginine(100 g/L,10 μL,n=8)and L-NAME (54.0 g/L,5 μL,n=12) had no significant effect on OT basal secretion.However,the elevated OT secretion in response to hypotension induced by intravenous infusion of sodium nitroprusside was dose-dependently augmented by icv injection of 5 μL L-NAME (dose 1:27.0 g/L,n=9；dose 2:54.0 g/L,n=8).The results indicate that L-NAME does not change basal OT secretion,but enhances OT reflex secretion evoked by hypotension,which suggests that NO may act as an inhibitory factor on reflex release of OT.