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Background <p>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 <i>(ASXL1)</i> gene function leads to a significantly enlarged spleen volume, due to an increased infiltration of myeloid cells into the spleen.</p> Methods <p>In 58 de novo AML patients presenting with splenomegaly at diagnosis, we evaluated the occurrence of <i>ASXL1</i> 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.</p> Results <p><i>ASXL1</i> mutations (<i>ASXL1</i>mut) were detected in 23/58 (40%) patients, being the most frequently mutated gene, followed by <i>TET2</i> and <i>NRAS</i>. <i>ASXL1</i>mut cases were significantly older than <i>ASXL1</i>wt (71 vs 64&#xa0;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 <i>ASXL1</i>mut subset compared to <i>ASXL1</i>wt (36.4% vs 72,1%, p = 0.002). Comparing the gene expression profile of the <i>ASXL1</i>mut and <i>ASXL1</i>wt groups, we found the upregulation of <i>PCDHB2</i> and <i>LURAP1L/LURAP1L-AS1</i> (all involved in mechanisms of cellular interaction and migration) genes in the former group, unveiling a role in the splenic infiltration of <i>ASXL1</i>mut leukemic cells.</p> Conclusions <p>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.</p>

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Splenomegaly in de novo acute myeloid leukemia is associated with ASXL1 mutations together with a distinct clinical and gene expression profile

  • 期刊论文

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  • 发表日期：

    2025年10月22日

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  • Francesco Tarantini,
  • Nicoletta Coccaro,
  • Cosimo Cumbo,
  • Immacolata Redavid,
  • Luisa Anelli,
  • Antonella Zagaria,
  • Elisa Parciante,
  • Maria Rosa Conserva,
  • Giuseppina Tota,
  • Crescenzio Francesco Minervini,
  • Angela Minervini,
  • Mariano Francesco Caratozzolo,
  • Flaviana Marzano,
  • Claudia Telegrafo,
  • Bachir Balech,
  • Anna Mestice,
  • Vito Pier Gagliardi,
  • Mario Delia,
  • Paola Carluccio,
  • Maria Giovanna Macchia,
  • Apollonia Tullo,
  • Giorgina Specchia,
  • Pellegrino Musto,
  • Francesco Albano

摘要

Background

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.

Methods

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.

Results

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.

Conclusions

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.