{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["13(1)"],"submitter":["Tarantini F"],"pubmed_abstract":["<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."],"journal":["Biomarker research"],"pagination":["131"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12542016"],"repository":["biostudies-literature"],"pubmed_title":["Splenomegaly in de novo acute myeloid leukemia is associated with ASXL1 mutations together with a distinct clinical and gene expression profile."],"pmcid":["PMC12542016"],"pubmed_authors":["Macchia MG","Albano F","Specchia G","Tota G","Carluccio P","Musto P","Anelli L","Zagaria A","Minervini A","Marzano F","Tarantini F","Minervini CF","Balech B","Redavid I","Coccaro N","Caratozzolo MF","Mestice A","Telegrafo C","Gagliardi VP","Delia M","Conserva MR","Parciante E","Tullo A","Cumbo C"],"additional_accession":[]},"is_claimable":false,"name":"Splenomegaly in de novo acute myeloid leukemia is associated with ASXL1 mutations together with a distinct clinical and gene expression profile.","description":"<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.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-06-05T04:30:29.982Z","creation":"2026-05-13T14:24:48.594Z"},"accession":"S-EPMC12542016","cross_references":{"pubmed":["41126357"],"doi":["10.1186/s40364-025-00833-8"]}}