Germline DDX41 variants have been implicated in late-onset myeloid neoplasms (MNs). Despite an increasing number of publications, many important features of DDX41-mutated MNs remain to be elucidated. Here, enrolling a total of 346 patients with DDX41 pathogenic/likely pathogenic (P/LP) germline variants and/or somatic mutations from 9,082 MN patients, together with 525 first-degree relatives of DDX41-mutated and wild-type (WT) patients, we performed a comprehensive characterization of DDX41-mutated MNs. P/LP DDX41 germline variants explained ~80% of known germline predisposition to MNs in adults. These risk variants were 10-fold more enriched in Japanese MN cases (n=4,461) compared to a Japanese general population (n=20,238). This enrichment of DDX41 risk alleles was much more prominent in male than female (20.7 vs. 5.0). P/LP DDX41 variants conferred a large risk of developing MNs, which was negligible until 40 years old but rapidly increased to 49% by 90 years of age. DDX41-mutated MDS patients rapidly progressed to AML, which was, however, confined to those having truncating variants. Co-mutation patterns at diagnosis and at progression to AML were substantially different between DDX41-mutated and -WT cases, where none of the co-mutations affected clinical outcomes. Even TP53 mutations made no exceptions and their dismal effect, including multi-hit allelic status, on survival was almost completely mitigated by the presence of DDX41 mutations. Finally, outcomes were not affected by the conventional risk stratifications including the revised/molecular International Prognostic Scoring System (IPSS-R/M). Our findings establish that DDX41-mutated MDS defines a unique subtype of MNs that is distinct from other MNs.

It has been shown on the dephosphorization ofliquid iron that the values oflog ƒÁP2o•B or log(ƒÁP2o5/ ƒÁ5Feo)at 1873K calculated from the data independently investigated and recently reported are closely related to those of the theoretical optical basicity for each slag, and these relations can be expressed in a simple single line for the case, in which slag constituents are lime, sodium oxide and several other materials. The symbol"ƒÁ"signifies the activity coefficient of slag components in mole fraction unit. The relation between the phosphate capacity and ƒÁP2o5 or optical basicity was also discussed. The phosphorus distribution between eleven kinds of slags and liquid CuP alloys given by Young and Floridis was analysed by the same way. It would be possible by calculation to estimate a slag composition suitable for dephosphorization, having high theoretical optical basicity.

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