BACKGROUND Gaucher disease (GD) is caused by a GBA1 gene mutation that leads to decreased acid β-glucosidase activity [glucocerebrosidase (GCase)]. This study aimed to identify and characterise compound heterozygous mutations in GBA1 in a patient with type 1 GD. CASE SUMMARY Here, we report a rare adult-onset type 1 GD in a 46-year-old female patient with clinical manifestations of giant spleen, thrombocytopenia, and bone pain, diagnosed by enzymatic and genetic testing. Enzymology and whole exome sequencing revealed heterozygous missense mutations in exon 10 c.1448T>C (p.L483P) and exon 7 c.928A>G (p.S310G) of GBA1 . The latter was first reported in patients with GD. Structural modelling showed that p.S310G and p.L483P were distant from the GCase active site. The p.S310G mutation in domain 1 may decrease stability between the α2 and α3 helices of GBA1 . The p.L483P mutation in domain 2 reduced the van der Waals force of the side chain and disrupted the C-terminal β-sheet. The patient was treated with imiglucerase replacement therapy, and her condition was stable. CONCLUSION The p.L483P/p.S310G novel compound heterozygous mutation underlies type 1 GD and likely affects GCase protein function. This is the first description of p.S310G being associated with mild type 1 GD in the context of a coinherited p.L483P mutation.

Objectives Platelet (PLT) recovery after chemotherapy is associated with the prognosis of patients with acute myeloid leukaemia (AML). This study aimed to explore the prognostic significance of early high PLT values in patients with de novo non‐M3 AML who achieved first complete remission (CR). Methods A total of 206 patients with de novo non‐M3 AML were analysed in this retrospective study. A receiver operating characteristic (ROC) curve was used to determine the optimal PLT cut‐off. The overall survival (OS) and relapse‐free survival (RFS) were assessed using Kaplan‐Meier and Cox regression analyses. Results 312×109/L was confined as the cut‐off of the PLT count. The estimated 3‐year OS of patients with high PLT was higher than that of their counterparts (72.3% vs. 34.6%, p = 0.001). In subgroup analysis, patients with high PLT had better OS in the favourable‐ and intermediate‐risk (non‐adverse‐risk) AML (p = 0.001). The estimated 3‐year RFS for the high and low PLT groups was 75.1% and 45.7% respectively (p = 0.078). Multivariate analyses revealed that high PLT count was an independent favourable variable for OS (HR = 0.264, p < 0.001) and RFS (HR = 0.375, p = 0.011) in the non‐adverse‐risk group. Conclusion Our results showed that early high PLT count recovery at first CR in non‐adverse‐risk AML patients is a positive prognostic marker for survival outcomes.

Background Gaucher disease (GD) is a rare autosomal recessive hereditary lysosomal storage disease. It is caused by glucocerebrosidase (GBA1) gene mutation that leads to decreased activity of acid β-glucosidase (glucocerebrosidase [GCase]). GD genotype-phenotype correlation is not fully understood. The aim of the current study was to identify and characterize compound heterozygous mutations of GBA1 in a type 1 adult GD patient. Results Using enzymological studies and whole exome sequencing, the patient with type 1 GD was found to becompound heterozygous for GBA1 missense mutations in exon 10 c.1448T > C (p.L483P) and exon 7 c.928A > G (p.S310G). The patient's mother who had Parkinson disease history was heterozygous for p.S310G mutation. The asymptomatic father was heterozygous for p.L483P mutation. The sister did not carry either mutation. Structural modeling showed both p.S310G and p.L483P are far away from the GCase active site. The p.S310G mutation in domain 1 could cause decreased stability between the α2 and α3 helices of GBA1. The p.L483P mutation in domain 2 could reduce the van der Waals force of the side chain and disrupt the C-terminal -sheet. Conclusions The p.L483P/p.S310G novel compound heterozygous mutation underlies type 1 GD and likely impacts GCase protein function. This is the first description of p.S310G associated with mild type 1 GD in the context of coinherited p.L483P mutation.

Platelet (PLT) recovery after chemotherapy is associated with the prognosis in patients with acute myeloid leukemia (AML); however, its predictive value is yet controversial. A total of 206 de novo non-M3 AMLs treated at the Second Affiliated Hospital of Shanxi Medical University from January 2014 to December 2020 and achieved complete remission (CR) were analyzed in this retrospective study. The overall survival (OS) and relapse-free survival (RFS) were assessed using Kaplan-Meier and Cox regression analyses.According to receiver operating characteristic (ROC) curve analysis, 312×10 9/L was confined as the cutoff of the PLT count, and hence, we divided patients into high PLT group (≥312×10 9/L) and low PLT group (100≤PLT&lt;312×10 9/L). Multivariate analysis revealed that early (we defined the highest PLT count from 28-42 days after induction chemotherapy as early platelet count and called it D28 PLT) high PLT count (≥312×10 9/L) recovery showed favorable RFS (hazard ratio (HR)=0.409, p=0.001) and OS (HR=0.394, p=0.001). The subgroup analysis demonstrated that patients in the favorable- and intermediate-risk (non-adverse-risk ) group with D28 PLT≥312×10 9/L showed better survival outcomes (RFS: HR=0.289, p=0.001; OS: HR=0.266, p&lt;0.001) compared to those with 100≤PLT&lt;312×10 9/L. The current study showed that early high PLT count recovery at CR in non-adverse-riskAMLs is an independent positive predictive factor for survival outcomes. Disclosures No relevant conflicts of interest to declare.