biostudies-literatureUnknown13(1)Tarantini F<h4>Background</h4>Splenomegaly is an event occurring in a variable range between 10-40% of de novo acute myeloid leukemia (AML), recently linked to poorer prognosis. Studies in murine models have shown that loss of the additional sex combs-like 1 (ASXL1) gene function leads to a significantly enlarged spleen volume, due to an increased infiltration of myeloid cells into the spleen.<h4>Methods</h4>In 58 de novo AML patients presenting with splenomegaly at diagnosis, we evaluated the occurrence of ASXL1 somatic mutations, deepened the molecular profile and conducted high-throughput RNA sequencing, with the aim of unveiling possible peculiar aspects of this rare clinical scenario.<h4>Results</h4>ASXL1 mutations (ASXL1mut) were detected in 23/58 (40%) patients, being the most frequently mutated gene, followed by TET2 and NRAS. ASXL1mut cases were significantly older than ASXL1wt (71 vs 64 years old, p = 0.003), showed a significantly higher white blood cells count (31,970/uL vs 17,810/uL, p = 0.044) and a higher platelet count (177,700/uL vs 67,700/uL, p = 0.0006). In contrast, the median bone marrow blasts percentage was lower in the ASXL1mut subset compared to ASXL1wt (36.4% vs 72,1%, p = 0.002). Comparing the gene expression profile of the ASXL1mut and ASXL1wt groups, we found the upregulation of PCDHB2 and LURAP1L/LURAP1L-AS1 (all involved in mechanisms of cellular interaction and migration) genes in the former group, unveiling a role in the splenic infiltration of ASXL1mut leukemic cells.<h4>Conclusions</h4>Overall, our data paves the way for further studies of an AML subgroup with a distinctive phenotype, whose prompt identification could improve patient management and therapeutic decision making.Biomarker research131https://www.ebi.ac.uk/biostudies/studies/S-EPMC12542016biostudies-literatureSplenomegaly in de novo acute myeloid leukemia is associated with ASXL1 mutations together with a distinct clinical and gene expression profile.PMC12542016Macchia MGAlbano FSpecchia GTota GCarluccio PMusto PAnelli LZagaria AMinervini AMarzano FTarantini FMinervini CFBalech BRedavid ICoccaro NCaratozzolo MFMestice ATelegrafo CGagliardi VPDelia MConserva MRParciante ETullo ACumbo CfalseSplenomegaly in de novo acute myeloid leukemia is associated with ASXL1 mutations together with a distinct clinical and gene expression profile.<h4>Background</h4>Splenomegaly is an event occurring in a variable range between 10-40% of de novo acute myeloid leukemia (AML), recently linked to poorer prognosis. Studies in murine models have shown that loss of the additional sex combs-like 1 (ASXL1) gene function leads to a significantly enlarged spleen volume, due to an increased infiltration of myeloid cells into the spleen.<h4>Methods</h4>In 58 de novo AML patients presenting with splenomegaly at diagnosis, we evaluated the occurrence of ASXL1 somatic mutations, deepened the molecular profile and conducted high-throughput RNA sequencing, with the aim of unveiling possible peculiar aspects of this rare clinical scenario.<h4>Results</h4>ASXL1 mutations (ASXL1mut) were detected in 23/58 (40%) patients, being the most frequently mutated gene, followed by TET2 and NRAS. ASXL1mut cases were significantly older than ASXL1wt (71 vs 64 years old, p = 0.003), showed a significantly higher white blood cells count (31,970/uL vs 17,810/uL, p = 0.044) and a higher platelet count (177,700/uL vs 67,700/uL, p = 0.0006). In contrast, the median bone marrow blasts percentage was lower in the ASXL1mut subset compared to ASXL1wt (36.4% vs 72,1%, p = 0.002). Comparing the gene expression profile of the ASXL1mut and ASXL1wt groups, we found the upregulation of PCDHB2 and LURAP1L/LURAP1L-AS1 (all involved in mechanisms of cellular interaction and migration) genes in the former group, unveiling a role in the splenic infiltration of ASXL1mut leukemic cells.<h4>Conclusions</h4>Overall, our data paves the way for further studies of an AML subgroup with a distinctive phenotype, whose prompt identification could improve patient management and therapeutic decision making.2025-01-01T00:00:00Z2025 Oct2026-06-05T04:30:29.982Z2026-05-13T14:24:48.594ZS-EPMC125420164112635710.1186/s40364-025-00833-8