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

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)
• hematological malignancy
• high-risk group
• chromosome abnormality

Acknowledgements

The authors cordially thank the participants of this study and all those who supported this project for their valuable time and contributions to this research. Figures 1 and 2 have been created with BioRender.com.

Author contributions

A.A., write the full manuscript, create the outline, data collection, and figure creation; J.P.B., critical review; R.P.B., critical review; A.M.Z., critical review; S.S., critical review; M.S., create the outline, critical review, and supervision.

Ethical approval

Not applicable due to the nature of the article.

Consent form

All the authors waive the consent of publication to the Leukemia and Lymphoma Journal.

Disclosure statement

AA, JPB, RPB, and SS have no conflict of interest (COI) to declare. AMZ received research funding (institutional) from Celgene/BMS, AbbVie, Astex, Pfizer, Kura, Medimmune/AstraZeneca, Boehringer-Ingelheim, Incyte, Takeda, Novartis, Shattuck Labs, Geron, Foran, and Aprea. AMZ participated in advisory boards, and/or had a consultancy with and received honoraria from AbbVie, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Servier, Boehringer-Ingelheim, Novartis, Astellas, Daiichi Sankyo, Geron, Taiho, Seattle Genetics, Otsuka, BeyondSpring, Takeda, Ionis, Amgen, Janssen, Genentech, Epizyme, Syndax, Gilead, Kura, Chiesi, ALX Oncology, BioCryst, Notable, Orum, Mendus, Zentalis, Schrodinger, Regeneron, Syros, and Tyme. AMZ served on clinical trial committees for Novartis, AbbVie, Gilead, Syros, BioCryst, AbbVie, ALX Oncology, Kura, Geron, and Celgene/BMS. MS served on the advisory board for Novartis, Kymera, Sierra Oncology, GSK, Rigel, BMS, Sobi, and Syndax; consulted for Boston Consulting and Dedham group and participated in CME activity for Novartis, Curis Oncology, Haymarket Media and Clinical care options.

Additional information

Funding

This article did not receive any kind of funding.