B. De Moerloose MD, PhD

Genetic insights in ETV6/RUNX1-positive B-cell precursor acute lymphoblastic leukaemia

SUMMARY

Acute lymphoblastic leukaemia, a clinically and biologically heterogeneous disease, represents the most common malignant disease in childhood. Approximately 20–25% of B-cell precursor acute lymphoblastic leukaemia in childhood carry the cryptic chromosomal translocation t(12;21)(p13;q22). This translocation combines two transcription factors and essential regulators of normal haematopoiesis, ETV6 and RUNX1, into the fusion oncogene ETV6/RUNX1 (formerly known as TEL/AML1). Recent studies in various animal models have strengthened the view that ETV6/RUNX1-positive cells give rise to pre-leukemic clones with a differentiation block in the pro/pre-B stage of B-cell development that, after acquisition of additional mutations, may transform into full malignancy. Despite the favourable prognostic parameters of this B-cell precursor acute lymphoblastic leukaemia subgroup, relapse and resistance to chemotherapeutics do occur and increased knowledge of the molecular mechanisms underlying ETV6/RUNX1-driven leukaemia is essential to develop novel therapeutic strategies to selectively target ETV6/RUNX1-positive leukaemia. In this manuscript, an overview of the most recent genetic insights in ETV6/RUNX1-positive B-cell precursor acute lymphoblastic leukaemia is given.

(BELG J HEMATOL 2017;8(5):179–84)

Unravelling the biology of juvenile myelomonocytic leukaemia using transcriptomics

SUMMARY

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)

Novel molecular genetic insights in paediatric B-cell precursor acute lymphoblastic leukaemia

SUMMARY

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)

P76 PrimeFlow™ RNA Assay: a novel technique for single-cell expression analysis in heterogeneous cell populations

Juvenile myelomonocytic leukaemia: the quest for more specific therapies

Summary

Juvenile myelomonocytic leukaemia is a very rare, aggressive stem cell disorder predominantly affecting infants and young children. Current survival rates are disappointing and the only available curative therapy is haematopoietic stem cell transplantation. Over the last years, intensive research efforts elucidated a plethora of molecular aberrations involved in the pathogenesis of juvenile myelomonocytic leukaemia. Current investigations are mainly directed towards the complete unravelling of the molecular biology behind the disease in order to find more specific drugs. This review will focus on the diagnosis, genomic characterisation and the use of experimental therapies in juvenile myelomonocytic leukaemia.

(BELG J HEMATOL 2014; 5(4): 119–24)

Minimal residual disease quantification by PCR in childhood acute lymphoblastic leukaemia

Summary

In Belgium approximately 70 children are diagnosed with acute lymphoblastic leukaemia annually. For these children, the monitoring of minimal residual disease has an important prognostic value. The level of minimal residual disease during the first three months of therapy is used to recognise subgroups that differ substantially in outcome. Two techniques are used for minimal residual disease monitoring: the Genescan method and the allele specific oligonucleotide polymerase chain reaction. The Genescan method is a less sensitive method (10⁻³) but is fast and less expensive. The allele specific oligonucleotide polymerase chain reaction requires more time and budget but has a sensitivity of 10⁻⁴–10⁻⁵. Both techniques have proven their value in minimal residual disease monitoring in childhood acute lymphoblastic leukaemia.

(BELG J HEMATOL 2014;5(3):81–8)

Fatal Myceliophthora thermophila infection in a boy with acute myeloid leukaemia and cord blood stem cell transplantation

Introduction

We report a Myceliophthora thermophila infection in a boy who underwent haematopoietic (cord blood) stem cell transplantation as treatment for relapsed acute myeloid leukaemia. Despite neutrophil engraftment and maximal supportive treatment, the child died of multi-organ failure. Infections with environmental moulds are rare, but potentially disastrous in immunocompromised patients. Rapid diagnosis and early treatment is of upmost importance.

(BELG J HEMATOL 2014;5(2):60–3)