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Review
. 2024 Feb 27;14(3):309.
doi: 10.3390/life14030309.

Recent Advances towards the Understanding of Secondary Acute Myeloid Leukemia Progression

Scott Auerbach  1 , Beana Puka  1 , Upendarrao Golla  2 , Ilyas Chachoua  1
Affiliations
Review

Recent Advances towards the Understanding of Secondary Acute Myeloid Leukemia Progression

Scott Auerbach et al. Life (Basel). .

Abstract

Secondary acute myeloid leukemia (sAML) is a heterogeneous malignant hematopoietic disease that arises either from an antecedent hematologic disorder (AHD) including myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), aplastic anemia (AA), or as a result of exposure to genotoxic chemotherapeutic agents or radiotherapy (therapy related AML, tAML). sAML is diagnosed when the number of blasts is ≥20% in the bone marrow or peripheral blood, and it is characterized by poor prognosis, resistance to therapy and low overall survival rate. With the recent advances in next generation sequencing technologies, our understanding of the molecular events associated with sAML evolution has significantly increased and opened new perspectives for the development of novel therapies. The genetic aberrations that are associated with sAML affect genes involved in processes such as splicing, chromatin modification and genome integrity. Moreover, non-coding RNAs' emerged as an important contributing factor to leukemogenesis. For decades, the standard treatment for secondary AML has been the 7 + 3 regimen of cytarabine and daunorubicin which prolongs survival for several months, but modifications in either dosage or delivery has significantly extended that time. Apart from traditional chemotherapy, hematopoietic stem cell transplantation, CAR-T cell therapy and small molecule inhibitors have also emerged to treat sAML.

Keywords: 7 + 3 regimen; AHD; AlloSCT; CAR-T; HSC; LSC; MDS; MPN; sAML; tAML.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of mutations, abnormalities and factors driving different hematological disorders and their progression to AML/sAML. Red: chromosomal abnormalities, blue: gene mutations, purple: therapeutic agents [10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26].
Figure 2
Figure 2
Pie chart displaying estimated proportions of sAML patients by history based on studies monitoring leukemic transformation. Each color represents the proportion of sAML patients by class. Percentages based on average incidence per 100,000 people.
Figure 3
Figure 3
A comprehensive schematic representing several classes of drugs and their mode of action for sAML treatment.
Figure 4
Figure 4
A diagram illustrating alloSCT (left) and CAR-T cell therapy (right) treatments for sAML.
See this image and copyright information in PMC

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References

    1. Estey E., Döhner H. Acute myeloid leukaemia. Lancet. 2006;368:1894–1907. doi: 10.1016/S0140-6736(06)69780-8. - DOI - PubMed
    1. Higgins A., Shah M.V. Genetic and genomic landscape of secondary and therapy-related acute myeloid leukemia. Genes. 2020;11:749. doi: 10.3390/genes11070749. - DOI - PMC - PubMed
    1. Pedersen-Bjergaard J., Andersen M.K., Andersen M.T., Christiansen D.H. Genetics of therapy-related myelodysplasia and acute myeloid leukemia. Leukemia. 2008;22:240–248. doi: 10.1038/sj.leu.2405078. - DOI - PubMed
    1. McMullin M.F., Anderson L.A. Aetiology of Myeloproliferative Neoplasms. Cancers. 2020;12:1810. doi: 10.3390/cancers12071810. - DOI - PMC - PubMed
    1. Shahin O.A., Chifotides H.T., Bose P., Masarova L., Verstovsek S. Accelerated Phase of Myeloproliferative Neoplasms. Acta Haematol. 2021;144:484–499. doi: 10.1159/000512929. - DOI - PMC - PubMed