Sign in Subscribe
Cancer research

New Insights into Acute Myeloid Leukemia Mechanisms

Strategic Insights

— 1 min read

Researchers at Lund University, Sweden, have discovered distinct mechanisms of relapse in KMT2A-rearranged acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in infants and children. The study, published in Nature Communications, analyzed whole-genome and exome sequencing of 36 patients with relapsed ALL/AML and found that somatic alterations in drug-response genes were highly enriched in early relapse ALL. This research highlights the unique challenges in treating KMT2A-r ALL and AML, which evade therapy differently and provide insights into the mechanisms of relapse in this highly lethal form of pediatric acute leukemia.

Key Takeaways:

  • Somatic alterations in drug-response genes, including TP53 and IKZF1, were highly enriched in early relapse ALL (79% of cases).
  • A marked chemotherapy-exposure signature was detected for mutations in early relapse ALL but not in very early ALL or AML relapse.
  • The study found that longitudinal analyses could track residual leukemia cells, clonal drug responses, and the upcoming relapse.
  • The research highlights that KMT2A-r ALL and AML evade therapy differently and provide insights into the mechanisms of relapse.
  • The study was funded by Barncancerfonden, Cancerfonden, and Vetenskapsradet.
  • The researchers used whole-genome and exome sequencing of infants and children with relapsed ALL/AML (n = 36) and longitudinal deep-sequencing of 257 samples in 30 patients.
  • Mattias Pilheden, Division of Clinical Genetics, Dept. of Laboratory Medicine, Lund University, was the lead researcher on the project.
  • Additional authors on the study include Louise Ahlgren, Helena Sturesson, Guangchun Song, Michael P. Walsh, Minjun Yang, Maud Maillard, Huanbin Zhao, Zhongshan Cheng, Varsha Singh, Anders Castor, Cornelis Jan Pronk, Hanne Vibeke Marquart, Birgitte Lausen, Pauline Schneider, and G. Publisher.

Statistics:

  • 36 patients with relapsed ALL/AML were analyzed in the study.
  • 79% of early relapse ALL cases showed somatic alterations in drug-response genes.
  • 9-36 months after diagnosis, early relapse ALL accounted for 79% of cases with these alterations.
  • 257 samples were obtained through longitudinal deep-sequencing in 30 patients.
  • The study was funded by three organizations: Barncancerfonden, Cancerfonden, and Vetenskapsradet.

Sources:

  • NewsRx. Studies Conducted at Lund University on Acute Myeloid Leukemia Recently Reported (The genomic landscape of relapsed infant and childhood KMT2A-rearranged acute leukemia). Hematology Week. October 20, 2025; p 623.
  • The genomic landscape of relapsed infant and childhood KMT2A-rearranged acute leukemia. Nature Communications, 2025;16(1):8964.

Read more