TY - JOUR
T1 - AML with germline DDX41 variants is a clinicopathologically distinct entity with an indolent clinical course and favorable outcome
AU - Li, Peng
AU - White, Thomas
AU - Xie, Wei
AU - Cui, Wei
AU - Peker, Deniz
AU - Zeng, Gang
AU - Wang, Huan You
AU - Vagher, Jennie
AU - Brown, Sara
AU - Williams, Margaret
AU - Kovacsovics, Tibor
AU - Patel, Jay L.
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022/3
Y1 - 2022/3
N2 - Germline DDX41 variants in myeloid neoplasms (MNs) are not uncommon, and we explored the prevalence and characterized the clinical and pathologic features in a cohort of 3132 unrelated adult MN patients. By targeted next-generation sequencing, we identified 28 patients (20 men and 8 women) with pathogenic germline DDX41 variants who developed acute myeloid leukemia (AML), in which only 3 (11%) had a family history (FH) of MNs. A subacute clinical course of cytopenia (mean duration of 11.2 months, range 0–72 months) prior to the initial AML diagnosis was accompanied by a low blast count (median at 30%, range 20–70%) in hypocellular marrows (93% of all patients), in vast contrast to the typical proliferative subtypes of AML in the elderly. Most patients had a normal karyotype (75%) and acquired a second DDX41 variant (69%). A favorable overall survival (OS) was observed in comparison to that of common subtypes of AML with wild-type DDX41 in age-matched patients. Our study demonstrated that the frequent germline pathogenic DDX41 variants characterized a clinically distinct AML entity. Features characteristic of DDX41-mutated AML include male predominance, often lack of FH, indolent course, low proliferative potential, frequent somatic DDX41 variants, and a favorable OS.
AB - Germline DDX41 variants in myeloid neoplasms (MNs) are not uncommon, and we explored the prevalence and characterized the clinical and pathologic features in a cohort of 3132 unrelated adult MN patients. By targeted next-generation sequencing, we identified 28 patients (20 men and 8 women) with pathogenic germline DDX41 variants who developed acute myeloid leukemia (AML), in which only 3 (11%) had a family history (FH) of MNs. A subacute clinical course of cytopenia (mean duration of 11.2 months, range 0–72 months) prior to the initial AML diagnosis was accompanied by a low blast count (median at 30%, range 20–70%) in hypocellular marrows (93% of all patients), in vast contrast to the typical proliferative subtypes of AML in the elderly. Most patients had a normal karyotype (75%) and acquired a second DDX41 variant (69%). A favorable overall survival (OS) was observed in comparison to that of common subtypes of AML with wild-type DDX41 in age-matched patients. Our study demonstrated that the frequent germline pathogenic DDX41 variants characterized a clinically distinct AML entity. Features characteristic of DDX41-mutated AML include male predominance, often lack of FH, indolent course, low proliferative potential, frequent somatic DDX41 variants, and a favorable OS.
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U2 - 10.1038/s41375-021-01404-0
DO - 10.1038/s41375-021-01404-0
M3 - Article
C2 - 34671111
AN - SCOPUS:85117368929
SN - 0887-6924
VL - 36
SP - 664
EP - 674
JO - Leukemia
JF - Leukemia
IS - 3
ER -