AML

Pediatric AML (pedAML) is a heterogeneous cancer of childhood, compising multiple subtypes defined by various genetic and epigenetic aberrations with prognostic and therapeutic impact. Although cure rates for pedAML have now reached 80%, still 30% of patients relapse, due to the incomplete eradication of resistant leukemic stem cells (LSCs). In addition, quality-of-life is strongly impaired due to the intense chemotherapeutic regimens and in some cases stem cell transplantation. Therefore, it is imperative to further unravel the biology of pedAML to develop better risk-stratifying algorithms and targeted therapies that further increase the cure rates with fewer long-term toxic side effects. To this end, our research team investigates the molecular basis of childhood AML as a prerequisite for the identification of novel therapeutic targets and stratification biomarkers to further improve the treatment and overall survival of children diagnosed with AML.

 

Over the past years our research group has undertaken transcriptome profiling in bulk and sorted (blast and LSC) AML samples, in order to identify novel therapeutic targets for the eradication of both leukemic blasts and LSC in pedAML. We have developed treatment options including specific cytotoxic T-cells showing promising results in vitro which are currently validated in vivo. Specifically, following the identification of TARP, a novel therapeutic target in AML, we have been able to generate TARP-directed therapy (cytotoxic T-cells and nanobodies)  illustrated the therapeutic value (Vanhooren et al., 2021; Depreter et al., 2020; Depreter et al., 2020). Moreover, therapeutic potential of novel targets was also investigated or is currently ongoing for EMP1 (Van Camp et al., 2024) and NID1, respectively.

Previous research has mainly studied the protein-coding part of the human genome, but recently the focus has also shifted to non-coding genes. We have also explored the non-coding transcriptome of AML. This resulted in an unique set of LSC- and leukemic blast-specific long non-coding RNA (lncRNA) who are currently futher investigated (Vanhooren et al., 2022).   Finally, we recently established a novel lncRNA expression signature, that allows to predict relapse-free survival in pedAML (Ren et al., 2024). 

Further advancements in technology, including mass spectrometry allow us also to investigate beyond the genome exploring histone post-translational modifications and proteins as the final arbiters of biological phenotypes. As the disease phenotype emerges from the intricate interplay of diverse molecular players, we believe a comprehensive -omics integration for a well-selected cohort of pedAML patients is essential to further refine and understand its pathobiology. Integrating genomic, transcriptomic, proteomic and epigenomic data will allow us to refine or redefine pedAML subtypes based on underlying biology, and will lead to novel therapeutic strategies to explore.

Finally, during the past years we have established a respository of AML patient-derived xenografts at Ghent University Hospital. This will allow us and collaborating research teams, to perform extensive in vivo evaluations of novel therapeutics.  

Publications

Ren Z,  Vanhooren J, Derpoorter C, De Moerloose B and Lammens T. (2024). “A 69 Long Non-Coding RNA Signature Predicts Relapse and Acts as Independent Prognostic Factor in Pediatric AML. Blood Advances. DOI: 10.1182/bloodadvances.2024012667. PMID: 38640434

Van Camp L, Depreter B, De Wilde J, Hofmans M, Terras E, Chantrain C, Dedeken L, Van Damme A, Uyttebroeck A and Lammens T. (under review). EMP1 in pediatric acute myeloid leukemia: to target or not to target?

Vanhooren JVan Camp L, Depreter B, de Jong M, Uyttebroeck A, Van Damme A, Dedeken L, Dress MF, van der Werff ten Bosch J, Hofmans M, Philippé J, De Moerloose B and Lammens T. (2022). Deciphering the non-coding landscape of pediatric acute myeloid leukemia. Cancers 14: 2098. DOI: 10.3390/cancers14092098  PMID: 35565228

Vanhooren JDerpoorter C, Depreter B, Deneweth L, Philippé J, De Moerloose B and Lammens T. (2021). TARP as antigen in cancer immunotherapy. Cancer Immunol. Immunother. 70 (11): 3061 – 3068. DOI: 10.1007/s00262-021-02972-x. PMID: 34050774

Depreter B, Weening K, Vandepoele K, Essand M, De Moerloose B, Themeli M, Cloos J, Hanekamp D, Moors I, D’hont I, Denys B, Uyttebroeck A, Van Damme A, Dedeken L, Snauwaert S, Goetgeluk G, De Munter S, Kerre T, Vandekerckhove B, Lammens T* and Philippé J*. (2020). TARP is an immunotherapeutic target in acute myeloid leukemia expressed in the leukemic stem cell compartment. Haematologica 105(5): 1306-1316. DOI: 10.3324/haematol.2019.222612. (* Both authors contributed equally). PMID: 31371409

Depreter B, De Moerloose B, Vandepoele K, Uyttebroeck A, Van Damme A, Denys B, Dedeken, L,  Dresse MF, Van der Werff Ten Bosch J, Hofmans M, Kerre T, Vandekerckhove B, Philippé J and Lammens  T. (2020). Clinical significance of TARP expression in pediatric acute myeloid leukemia. Hemasphere 4 (2): e346. DOI: 10.1097/HS9.0000000000000346. PMID: 32309783