Table 1. Description of HMs arising from... | American Society of Hematology

Table 1.

Description of HMs arising from deleterious germ line DDX41 variants in WHO classification vs recent updates

Topics	WHO classification	Updates by recent studies
Prevalence	1.5% of MNs	High in high-risk MDS/sAML (5%-8%), low in MPN (<1%)^1-9/10 times more enrichment in MNs¹
Germ line mutations	Half of all the mutations	70%-80%, two-thirds are truncating⁴^,^10-12
Age at onset	Long latency (mean 62 yo)	Long latency (mean 66 yo)^1-9^,¹¹^,^13-17
Male predominance	No description	Yes (1.7-3.1 times), compared with WT cases in any disease phenotype¹^,²^,¹⁴
Hematologic findings	Leukopenia/erythroid dysplasia	Hypocellular bone marrow/higher blast count in MDS¹
Penetrance	Not fully established	0% of penetrance at 40 yo/50% lifelong penetrance¹
Karyotype	Frequent normal karyotype	Normal karyotype is 2-4 times more frequent, compared with WT cases¹^,⁷^,¹³^,¹⁴
Concomitant mutations	No description	Mutations in CUX1 and GNAS are more frequent compared with WT cases¹^, Mutations in ASXL1, TET2, DNMT3A, and TP53 are frequent but the frequencies are not significantly different compared with those in WT cases¹^,²^,⁷^,¹⁸
Leukemic evolution	No description	Faster leukemic evolution¹^,¹⁹
Prognosis	Poor in cases with somatic deletion	Better in cases with pathogenic variants¹^,²^,⁴^,¹⁴^,¹⁷^,²⁰
Therapeutics	Lenalidomide may be effective	Hypomethylating agents may be effective¹

Topics	WHO classification	Updates by recent studies
Prevalence	1.5% of MNs	High in high-risk MDS/sAML (5%-8%), low in MPN (<1%)^1-9/10 times more enrichment in MNs¹
Germ line mutations	Half of all the mutations	70%-80%, two-thirds are truncating⁴^,^10-12
Age at onset	Long latency (mean 62 yo)	Long latency (mean 66 yo)^1-9^,¹¹^,^13-17
Male predominance	No description	Yes (1.7-3.1 times), compared with WT cases in any disease phenotype¹^,²^,¹⁴
Hematologic findings	Leukopenia/erythroid dysplasia	Hypocellular bone marrow/higher blast count in MDS¹
Penetrance	Not fully established	0% of penetrance at 40 yo/50% lifelong penetrance¹
Karyotype	Frequent normal karyotype	Normal karyotype is 2-4 times more frequent, compared with WT cases¹^,⁷^,¹³^,¹⁴
Concomitant mutations	No description	Mutations in CUX1 and GNAS are more frequent compared with WT cases¹^, Mutations in ASXL1, TET2, DNMT3A, and TP53 are frequent but the frequencies are not significantly different compared with those in WT cases¹^,²^,⁷^,¹⁸
Leukemic evolution	No description	Faster leukemic evolution¹^,¹⁹
Prognosis	Poor in cases with somatic deletion	Better in cases with pathogenic variants¹^,²^,⁴^,¹⁴^,¹⁷^,²⁰
Therapeutics	Lenalidomide may be effective	Hypomethylating agents may be effective¹

MPN, myeloproliferative neoplasm; WT, wild-type.