Acute myeloid leukemia (AML) with chromosome 3 inversion: biology, management, and clinical outcome

Leuk Lymphoma. 2024 Nov;65(11):1541-1551. doi: 10.1080/10428194.2024.2367040. Epub 2024 Jul 4.

Abstract

Acute myeloid leukemia (AML) is a complex hematological malignancy characterized by diverse genetic alterations, each with distinct clinical implications. Chromosome 3 inversion (inv(3)) is a rare genetic anomaly found in approximately 1.4-1.6% of AML cases, which profoundly affects prognosis. This review explores the pathophysiology of inv(3) AML, focusing on fusion genes like GATA2::EVI1 or GATA2::MECOM. These genetic rearrangements disrupt critical cellular processes and lead to leukemia development. Current treatment modalities, including intensive chemotherapy (IC), hypomethylating agents (HMAs) combined with venetoclax, and allogeneic stem cell transplantation are discussed, highlighting outcomes achieved and their limitations. The review also addresses subgroups of inv(3) AML, describing additional mutations and their impact on treatment response. The poor prognosis associated with inv(3) AML underscores the urgent need to develop more potent therapies for this AML subtype. This comprehensive overview aims to contribute to a deeper understanding of inv(3) AML and guide future research and treatment strategies.

Keywords: Acute myeloid leukemia (AML); chromosome abnormality; hematological malignancy; high-risk group.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Chromosome Inversion*
  • Chromosomes, Human, Pair 3* / genetics
  • Combined Modality Therapy / methods
  • Disease Management*
  • Humans
  • Leukemia, Myeloid, Acute* / diagnosis
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / therapy
  • Oncogene Proteins, Fusion / genetics
  • Prognosis
  • Treatment Outcome

Substances

  • Oncogene Proteins, Fusion