MLLT10 and Acute Myeloid Leukemia

The association between MLLT10 (HGNC:16063) and acute myeloid leukemia (MONDO_0018874) is supported by multiple independent clinical studies. Case reports and multi‐patient studies have identified recurrent fusion events involving MLLT10 in patients with AML, including both pediatric and adult cases. In one report, a novel MLL-AF10 fusion mRNA transcript was detected in a pediatric patient using an advanced asymmetric reverse transcription PCR method (PMID:9305618), while additional studies have confirmed the presence of MLLT10 rearrangements in AML cohorts using cytogenetic and molecular approaches (PMID:11911106, PMID:30227397).

Genetic evidence indicates that these fusion events occur as somatically acquired rearrangements and are observed across diverse patient populations. Although there is no classical family segregation, recurrent detection in independent cases provides robust support for the gene-disease association. Overall, more than 25 probands carrying MLLT10 rearrangements have been documented across the literature (PMID:30624859, PMID:34551411).

No valid HGVS coding variant meeting the selection criteria for MLLT10 was identified in the supplied evidence, as the published alterations primarily consist of fusion transcripts. Therefore, the detailed molecular description relies on cytogenetic breakpoints and fusion analysis rather than a singular point mutation or indel. This does not detract from the strength of the overall genetic evidence linking MLLT10 to AML.

Functional evidence remains limited in scope. Direct experimental studies investigating the impact of MLLT10 rearrangements on leukemogenesis are sparse. However, the fusion proteins generated by these rearrangements are inferred to drive pathogenicity via transcriptional dysregulation, a mechanism that is consistent with established models of oncogenesis in AML.

There is no significant conflicting evidence reported in the provided studies. All available data converge on the clinical relevance of MLLT10 rearrangements in the pathogenesis of acute myeloid leukemia.

In summary, the body of evidence from multiple case reports and large clinical cohorts supports a strong gene-disease association between MLLT10 and AML. This integration of genetic findings and mechanistic insight reinforces the clinical utility of screening for MLLT10 rearrangements in diagnostic decision‑making and has important implications for patient stratification and targeted therapies.

Key Take‑home: MLLT10 rearrangements represent a robust biomarker in AML that can guide clinical diagnosis and therapeutic strategies.

References

• Leukemia • 1997 • A novel MLL-AF10 fusion mRNA variant in a patient with acute myeloid leukemia detected by a new asymmetric reverse transcription PCR method PMID:9305618
• Acta haematologica • 2018 • Mediastinal Myeloid Sarcoma with TP53 Mutation Preceding Acute Myeloid Leukemia with a PICALM-MLLT10 Fusion Gene PMID:30227397
• Leukemia & lymphoma • 2002 • Incidence of MLL rearrangement in acute myeloid leukemia, and a CALM-AF10 fusion in M4 type acute myeloblastic leukemia PMID:11911106
• International journal of laboratory hematology • 2019 • Acute myeloid leukemia with t(10;11)(p11-12;q23.3): Results of Russian Pediatric AML registration study PMID:30624859
• Acta haematologica • 2022 • Adult Acute Myeloid Leukemia with the KMT2A-Mixed Lineage Leukemia T10 Fusion: An Analysis of 10 Cases Showed Common Features and Frequent Mutations in the RAS Signaling Pathway PMID:34551411

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