In Pursuit of Genetic Prognostic Factors and Treatment Approaches in Secondary Acute Myeloid Leukemia—A Narrative Review of Current Knowledge

Abstract

Secondary acute myeloid leukemia can be divided into two categories: AML evolving from the antecedent hematological condition (AHD-AML) and therapy related AML (t-AML). AHD-AML can evolve from hematological conditions such as myelodysplastic syndromes, myeloproliferative neoplasms, MDS/MPN overlap syndromes, Fanconi anemia, and aplastic anemia. Leukemic transformation occurs as a consequence of the clonal evolution—a process of the acquisition of mutations in clones, while previous mutations are also passed on, leading to somatic mutations accumulation. Compared de novo AML, secondary AML is generally associated with poorer response to chemotherapy and poorer prognosis. The therapeutic options for patients with s-AML have been confirmed to be limited, as s-AML has often been analyzed either both with de novo AML or completely excluded from clinical trials. The treatment of s-AML was not in any way different than de novo AML, until, that is, the introduction of CPX-351—liposomal daunorubicin and cytarabine. CPX-351 significantly improved the overall survival and progression free survival in elderly patients with s-AML. The only definitive treatment in s-AML at this time is allogeneic hematopoietic cell transplantation. A better understanding of the genetics and epigenetics of s-AML would allow us to determine precise biologic drivers leading to leukogenesis and thus help to apply a targeted treatment, improving prognosis.

Transforming growth factor-β1 and vascular endothelial growth factor levels in senile acute myeloid leukemia and correlation with prognosis

“…TGFβ1 can enhance leukemia cell invasion and metastasis, thereby contributing to disease progression and worse prognosis. According to Stefaniuk et al [ 30 ], TGFβ1 can promote leukemia cell motility and adhesion, as well as extracellular matrix degradation and angiogenesis, thereby promoting metastasis in leukemia. By modulating immune responses, TGFβ1 can also facilitate the survival and progression of leukemia cells.…”

Characterization and prognostic factors of secondary to MDS/MPN and therapy-related AML: a single-center study

“…Great expectations rest on the use of immune check-points [nivolumab (NCT02532231), pembrolizumab (NCT04284787)], IDH inhibitors -ivosidenib (NCT03173248, NCT02632708), enasidenib (NCT02632708), and targeted drugs for spliceosomes (NCT04278768) or bromodomain and extra-terminal domain (BET) proteins -NCT02698189, which unfortunately was terminated due to limited efficacy [2]. The literature indicates that therapy with chimeric antigen receptor-T (CAR-T) may also play a role in sAML [39][40][41].…”

Myeloid neoplasms post cytotoxic therapy: epidemiology, pathogenesis outcomes, prognostic factors, and treatment options

“…TP53 activation leads to the elimination or repair of damaged cells, in order to reduce the risk of propagating mutations. It is hypothesized that TP53 promotes a selective growth advantage after exposure to chemo- or radiotherapy, leading to out-competing cells with high p53 activity by those with reduced p53 activity [ 22 ]. MN-pCT patients with chromosome 7 abnormality often have RAS pathway activation-related mutations, which are also associated with poor prognosis [ 23 ].…”