Novel KMT2A fusion partner genes in acute leukemia—MRTFB, SORBS1, and SSC5D

Abstract

KMT2A (formerly MLL) gene rearrangements are common and clinically significant in acute leukemias, with outcomes influenced by the fusion partner. Over 100 fusion partners are known, but new ones continue to emerge. This study identifies three novel partners—myocardin-related transcription factor B (MRTFB), sorbin and SH3 domain-containing 1 (SORBS1), and scavenger receptor cysteine-rich family member with 5 domains (SSC5D)—in pediatric and adult acute leukemia cases. Three cases were analyzed: a boy with B-cell precursor acute lymphoblastic leukemia, a girl with acute myelomonocytic leukemia, and a woman with therapy-related acute myeloid leukemia (AML). Diagnostics included cytogenetic analysis, fluorescence in situ hybridization (FISH), multiplex reverse transcription-polymerase chain reaction (RT-PCR), whole genome sequencing (WGS), and confirmation of breakpoints by Sanger sequencing, with validation at DNA and RNA levels, using patient-specific primers. WGS identified three novel in-frame fusions: KMT2A::MRTFB, KMT2A::SORBS1, and KMT2A::SSC5D, all within the major KMT2A breakpoint region. All patients achieved complete remission with tailored therapy, including chemotherapy and hematopoietic stem cell transplantation where indicated. Follow-up demonstrated durable remissions ranging from 9 to 23 months at the time of reporting. This study expands the catalog of KMT2A fusion partners, highlighting MRTFB, SORBS1, and SSC5D as novel leukemia-associated genes. The findings underscore the value of WGS for comprehensive detection of rare genetic events, enabling improved molecular classification and prognostic assessment in KMT2A-rearranged leukemias.

Keywords

acute leukemia / fusion genes / KMT2A / cytogenetics / WGS

RIGHTS & PERMISSIONS

Higher Education Press 2026

Just Accepted

This article has successfully passed peer review and final editorial review, and will soon enter typesetting, proofreading and other publishing processes. The currently displayed version is the accepted final manuscript. The officially published version will be updated with format, DOI and citation information upon launch. We recommend that you pay attention to subsequent journal notifications and preferentially cite the officially published version. Thank you for your support and cooperation.