BJH - volume 9, issue 2, march 2018
E. Vanlancker ir, PhD, B. Vanhoecke PhD, B. De Moerloose MD, PhD, T. Van de Wiele ir, PhD
In this PhD thesis, we investigated the impact of chemotherapy on the microbiota in the context of mucositis by using different experimental set-ups. Using bacterial monocultures, we showed that exposure to 5-fluorouracil at physiologically relevant concentrations differentially impacts oral microorganisms. Despite this difference in microbial sensitivity to 5-fluorouracil in pure cultures, we showed that the impact of 5-fluorouracil, as well as irinotecan, towards highly diverse gastrointestinal microbial populations is only marginal. These findings were generated with two different model systems that exclude host cells and this led us to conclude that the host is crucial in the establishment of chemotherapy-induced shifts in microbial composition and functionality. The next step in our research entailed the use of an in vitro wound healing model, where we demonstrated that the presence of microbiota negatively impacts the wound healing capacity of damaged oral epithelial cells. This indicates that microbial presence can delay the recovery from mucositis. Yet, we also found that microbial composition, which is for instance disturbed in patients receiving cancer therapy, is an additional determinant of aggravated wound healing. We further substantiated this conclusion with an in vivo longitudinal monitoring study of paediatric patients treated for haematological malignancies. While shifts in the oral microbial community during and following chemotherapy were mostly patient-specific, clear associations were made with the use of systemic antibiotics and antibacterial mouth rinses, which create microbial dysbiosis. In view of these findings we propose that the preventive use of antimicrobials needs careful consideration given the profound impact on the microbiome and subsequent consequence for the host.
(BELG J HEMATOL 2018;9(2):68–70.)
Read moreBJH - volume 8, issue 7, december 2017
S.M. Aukema MD
On May 29th, 2017, Sietse M. Aukema defended his thesis, entitled ‘Role of MYC in paediatric and adult B-cell lymphoma patients’. His research was performed under the supervision of (hemato)pathologist Prof. P.M. Kluin, MD, PhD, and clinical geneticist Prof. R. Siebert, MD. The most important findings of his thesis are summarised in this report.
(BELG J HEMATOL 2017;8(7):276–8)
Read moreBJH - volume 8, issue 6, october 2017
S. Peirs PhD
Patients with T-cell acute lymphoblastic leukaemia are mainly treated with intensive combination chemotherapy. Although this treatment strategy is quite successful in children, refractory or relapsed disease is more difficult to treat. Moreover, the chemotherapeutic agents are associated with substantial toxicity. In order to find more effective and less toxic therapies, the genetic and epigenetic alterations in T-cell acute lymphoblastic leukaemia are studied and molecularly targeted drugs are being developed. In this thesis, two new strategies to treat T-cell acute lymphoblastic leukaemia were identified and evaluated. On the one hand, high expression of the anti-apoptotic factor BCL2 was found as a hallmark of the immature T-cell acute lymphoblastic leukaemia subgroup. The BCL-2 specific inhibitor venetoclax proved to be a promising potential new therapy in T-cell acute lymphoblastic leukaemia and synergized with standard chemotherapeutic agents and BET bromodomain inhibitors. On the other hand, the enzyme KDM1A was identified as an interaction partner of the oncogenic transcription factor ZEB2. Antileukemic effects were demonstrated in several T-cell acute lymphoblastic leukaemia cell lines upon pharmacological inhibition of KDM1A.
(BELG J HEMATOL 2017;8(6):244–6)
Read moreBJH - volume 8, issue 5, september 2017
H. Helsmoortel PhD, T. Lammens PhD, P. Van Vlierberghe PhD, B. De Moerloose MD, PhD
Juvenile myelomonocytic leukaemia is a rare and aggressive blood cancer occurring in early childhood. Research in the past decades mainly focused on identifying aberrations at the DNA level. Although our molecular knowledge about juvenile myelomonocytic leukaemia biology has steadily increased over the last years, haematopoietic stem cell transplantation is currently the only curative option. Unfortunately, the relapse rate after stem cell transplantation remains high and almost half of the children do not survive the disease, indicating that new therapeutic strategies are urgently required. To further elucidate the biology of the disease, we investigated gene expression levels of both coding and non-coding RNA molecules. This led to the identification of LIN28B and its co-regulated genes as central players in juvenile myelomonocytic leukaemia biology and opens the door for the development of new targeted therapeutics.
(BELG J HEMATOL 2017;8(5):198–200)
Read moreBJH - volume 8, issue 3, june 2017
F. Ghazavi PhD, T. Lammens PhD, P. Van Vlierberghe PhD, B. De Moerloose MD, PhD
Paediatric B-cell precursor acute lymphoblastic leukaemia arises from recurrent genetic lesions that block precursor B-cell differentiation and drive aberrant proliferation and cell survival. Risk-adapted intensive chemotherapy has been a major breakthrough in reaching the current survival rates of >90% for this ALL subtype. Recent developments in genome-wide genetic analysis have provided a wide range of chromosomal and genomic abnormalities characterising B-cell precursor acute lymphoblastic leukaemia, several of which are associated with patient outcome. This article summarises the results of several studies performed during the PhD thesis of Dr Farzaneh Ghazavi. This research project has led to the identification of a novel molecular lesion predicting poor outcome, a novel targetable pathway in a subgroup of B-cell precursor acute lymphoblastic leukaemia patients and resulted in the identification of an ETV6/RUNX1-specific long non-coding RNA signature providing novel biological insights into ETV6/RUNX1-mediated leukemogenesis.
(BELG J HEMATOL 2017;8(3):118–21)
Read moreBJH - volume 8, issue 2, march 2017
A.G. Dinmohamed PhD, MSc
The main aim of this thesis was to progress our understanding on different epidemiologic aspects of myelodysplastic syndromes and acute myeloid leukaemia at the population level in the Netherlands. These aspects include surveillance of the cancer burden, guideline adherence concerning diagnostics and therapy, and comparative effectiveness research. Population-based registries are useful instruments to study all patients within a well-defined area, so as to overcome patient selection which is always at hand in clinical intervention studies. The results described in this thesis provided a benchmark for incidence, diagnosis, treatment, trial participation and survival of myelodysplastic syndromes and acute myeloid leukaemia in the Netherlands. Future studies should provide insight whether clinical practice changed following the results described in this thesis.
(BELG J HEMATOL 2017;8(2):83–6)
Read moreBJH - volume 8, issue 2, march 2017
K. Durinck PhD
T-cell acute lymphoblastic leukaemia was originally identified as a highly aggressive blood disorder associated with poor prognosis, but intensified therapy has since led to remarkable improvements in survival. Unfortunately, these treatment regimens (mainly combination chemotherapy) are associated with severe acute and long-term toxicities. Moreover, the prognosis of patients with relapsed and refractory disease remains extremely poor. To shift towards a personalised medicine approach, a profound understanding of the molecular basis of the progression of this leukaemia subtype is required. This thesis discusses an integrative genomics approach to functionally dissect the interplay between established and novel transcriptional regulators that take part in the rewired transcriptional networks that drive malignant transformation of thymocytes to T-ALL lymphoblasts.
(BELG J HEMATOL 2017;8(2):80–2)
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