How to improve AML outcomes?

Abstract

Understanding the intricacies of the pathophysiology and genomic landscape has enhanced the long-term outcomes for patients with acute myeloid leukemia (AML). The identification of novel molecular targets has introduced new therapeutic strategies that attempt to surpass the dominance of the "7 + 3 regimen" established in the 1970s. In 2022, the World Health Organization and International Consensus Classification revised their definitions and approaches to AML, reflecting the current and evolving changes at the molecular level. The guidelines are now grounded in a definition of the disease that emphasizes genetic characteristics. Today, we recognize AML as a genetically diverse disease; a retrospective study identified 5234 driver mutations across 76 genes or genomic regions, with two or more drivers observed in 86% of patients (Papaemmanuil et al., N Engl J Med 374:2209-21, 2016).

Keywords: AML; Mutations; Outcome; Relapsed; Targeted; Treatment.

Fig. 1

Hierarchical classification of the International Consensus Classification of AML. AML—Acute Myeloid Leukemia, ASXL1—Additional Sex Combs Like 1, BCOR—BCL6 Corepressor, EZH2—Enhancer of Zeste Homolog 2, MDS—Myelodysplastic Syndrome, MPN—Myeloproliferative Neoplasm, RUNX1—Runt-Related Transcription Factor 1, SF3B1—Splicing Factor 3b Subunit 1, SRSF2—Serine/Arginine-Rich Splicing Factor 2, STAG2—Stromal Antigen 2, TP53—Tumor Protein 53, U2AF1—U2 Small Nuclear RNA Auxiliary Factor 1, VAF—Variant Allele Frequency, ZRSR2—Zinc Finger CCCH-Type, RNA-Binding Motif and Serine/Arginine-Rich 2

Fig. 2

2022 ELN risk classification by genetics at initial diagnosis. AML—Acute Myeloid Leukemia, ASXL1—Additional Sex Combs Like 1, BCOR—BCL6 Corepressor, CEBPA—CCAAT Enhancer Binding Protein Alpha, CREBBP—CREB Binding Protein, EZH2—Enhancer of Zeste Homolog 2, FLT3-ITD—FMS-like Tyrosine Kinase 3-Internal Tandem Duplication, GATA2—GATA Binding Protein 2, KMT2A—Lysine Methyltransferase 2A, MEF2C—Myocyte Enhancer Factor 2C, MLLT3—Myeloid/Lymphoid or Mixed-Lineage Leukemia Translocated to 3, MYH11—Myosin Heavy Chain 11, NPM1—Nucleophosmin 1, NUP214—Nucleoporin 214, RUNX1—Runt-Related Transcription Factor 1, SF3B1—Splicing Factor 3b Subunit 1, SRSF2—Serine/Arginine-Rich Splicing Factor 2, STAG2—Stromal Antigen 2, TP53—Tumor Protein 53, U2AF1—U2 Small Nuclear RNA Auxiliary Factor 1, ZRSR2—Zinc Finger CCCH-Type, RNA-Binding Motif and Serine/Arginine-Rich 2

Fig. 3

a b Treatment Algorithm for Newly diagnosed patients with AML fit for intensive therapy. AML—Acute Myeloid Leukemia, CBF—Core Binding Factor, CK—Complex Karyotype, CPX351—Liposomal Daunorubicin and Cytarabine, FLT3—FMS-like Tyrosine Kinase 3, GO—Gemtuzumab Ozogamicin, HMA—Hypomethylating Agents, tAML—Therapy-Related Acute Myeloid Leukemia, AML-MR—Acute Myeloid Leukemia with Myelodysplasia-Related Changes, TP53—Tumor Protein 53, Ven—Venetoclax