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Page 72 Leung et al. J Transl Genet Genom 2023;7:79-86 https://dx.doi.org/10.20517/jtgg.2023.09

profiles of these patients. Reportedly, the latter resulted in less frequent 30-day mortality and overall survival
[22]
compared with those patients receiving SOC . While the impact of this study remains to be seen, it
highlighted the potential application of genomic information in guiding the upfront treatment of AML.

Another approach to personalized treatment of AML involves in vitro testing of drug sensitivity, with the
goal of using the results to guide the clinical treatment of patients in real-time. This approach is akin to
culture and sensitivity testing that guides antibiotic treatment for infectious diseases in clinics. Interestingly,
leukaemia blasts grow very slowly ex vivo once they are taken out of their hosts, and optimization of culture
conditions becomes critical for their maintenance and evaluation of drug sensitivity. When coupled with
genomic information of the samples, in vitro drug sensitivity provides a powerful platform for identifying
novel biomarkers predictive of drug response and personalized treatment through drug repurposing. Using
these platforms, homoharringtonine was shown to be effective in FLT3-ITD AML through protein
translation inhibition . Importantly, clinical response to FLT3 inhibitors and homoharringtonine in
[23]
patients receiving such treatments were correlated with the in vitro drug sensitivity of their samples,
attesting to the potential application of the latter in predicting clinical responses. More recently, results from
in vitro drug sensitivity testing of blood and BM samples from AML patients with relapsed and refractory
disease against 515 anticancer drugs were used to guide the treatment of 37 patients using a customized
combination of 2-3 drugs based on patient-specific sensitivity to single drugs and molecular data.
Reportedly, nearly 60% of evaluable patients showed clinically meaningful responses, of whom the majority
[24]
achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi) . A similar
approach was also reported in pediatric AML patients .
[25]
Recent advances in transcriptomic analysis at the single-cell level have enabled the evaluation of cellular
heterogeneity and hierarchy in AML, as well as the simultaneous examination of non-leukemic immune cell
populations. It is now technically possible to enhance its analytic power by simultaneously measuring
immunophenotype using barcoded antibodies and epigenetic state based on single-cell ATAC-sequencing.
Bioinformatic analyses can enable the clustering of distinct cell populations based on their transcriptome
[26]
profile . Serial monitoring of the BM transcriptome upon leukaemia treatment at the single-cell level may
shed light on the therapeutic responses in the leukaemia and microenvironment compartments.

CONCLUSION
Recent advances in genome sequencing technologies have empowered scientists and clinicians with the
ability to examine inter-individual and intra-tumoral heterogeneities in acute myeloid leukaemia in great
detail. The information has begun to influence the clinical management and prognostication of the disease.
Transcriptome analyses at a single cell level are ideally suited to examine cellular heterogeneity in leukaemia
samples and will shed important light on the dynamic changes of the microenvironment in the course of
leukaemia therapy.

DECLARATIONS
Authors’ contributions
Performed the literature search and wrote the manuscript: Leung HC
Outlined the scope of the review and wrote the manuscript: Leung AYH

Availability of data and materials
Not applicable.