J. Philippé MD, PhD

Anaemia and its association with asymptomatic malaria, iron and zinc deficiencies, and Ferroportin Q248H mutation in children aged under five years in South Kivu, Democratic Republic of Congo

SUMMARY

Anaemia is a public health problem affecting one quarter of the global population with significant health consequences as well as an adverse impact on social and economic development. In malaria endemic areas, Plasmodium infection remains the major cause of anaemia. The ferroportin Q248H mutation has been described to protect red blood cells against oxidative stress and malaria infection. The objective of this study was to describe the main mechanisms causing anaemia and the role of ferroportin Q248H mutation in relation with anaemia and malaria in childhood in a Bantu population living in the volcanic region of South Kivu. 1088 healthy children aged under five years were randomly selected in the health zone of Miti Murhesa in South Kivu/Democratic Republic of Congo. Almost 40% of children under five years were anaemic, submicroscopic Plasmodium infection was as high as 22.3%. The prevalence of ferroportin Q248H mutation was 11.4%. No difference was observed in the frequencies of malaria or anaemia between ferroportin mutated compared to ferroportin wild type children. The prevalence of iron deficiency was found to be high (49.1%) when free erythrocyte protoporphyrin (FEP) was used to assess iron status. We found zinc deficiency in 17.6% of children. The prevalence of anaemia in South Kivu remains high, children with low parasitemia detected by loop mediated-isothermal amplification assay (LAMP) but not by microscopy showed a significantly increased prevalence of anaemia. Ferritin, an acute phase protein of infection is less suited to assess iron status in endemic areas of Plasmodium infection.

(BELG J HEMATOL 2022;13(7):281–3)

Novel therapeutic targets in juvenile myelomonocytic leukaemia: Are noncoding RNAs valuable treatment options?

SUMMARY

Juvenile myelomonocytic leukaemia is a rare and aggressive clonal disease of early childhood for which hematopoietic stem cell transplantation remains the only curative option, albeit with a high relapse rate and many associated toxicities. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) have recently been implicated in a variety of biological processes, including haematopoiesis and receive much research attention as they possess features interesting for treatment, such as tissue specificity, low overall expression and easy targetability with RNAi or gene editing technology. Within this dissertation, we aimed at deciphering the lncRNA and circRNA transcriptome of JMML and use this knowledge to develop novel treatments.

(BELG J HEMATOL 2021;12(4):173-6)

Retrospective analysis of the incidence and characteristics of paediatric myelodysplastic syndrome and juvenile myelomonocytic leukaemia in Belgium

SUMMARY

Childhood myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukaemia (JMML) are very rare clonal stem cell disorders of early childhood. Paediatric MDS can be further subdivided in refractory cytopenia of childhood (RCC) and high grade MDS, in case of excess blasts. Given their rarity, little is known about the epidemiology of these diseases in Belgium. The aim of this study is to investigate the incidence, characteristics, treatment and prognosis of paediatric MDS and JMML in Belgium. Prospectively collected data of 56 Belgian patients with MDS and JMML were enrolled in the study, of which 41 (73%) with MDS, eleven with JMML (20%) and four (7%) with Noonan syndrome associated myeloproliferative disorder. The incidence rates of MDS and JMML in Belgium were 1.5 and 0.4 per million children per year respectively, with a median age of diagnosis of 9.3 years for RCC, 9.5 years for high grade MDS and 2.6 years for JMML. Monosomy 7 was the most common cytogenetic abnormality and could particularly be found in high grade MDS (33%) and JMML (45%). RCC treatment consisted of immunosuppressive therapy (IST) and haematopoietic stem cell transplantation (HSCT), but in high grade MDS and JMML only HSCT was a valid treatment option. Overall survival was significantly lower in high grade MDS (45.0%) compared to JMML (79.5%) and RCC (80.6%) (log-rank p-value = 0.038), whereas event-free survival (EFS) was comparably low in high grade MDS and JMML (46.7% and 58.4% respectively) due to a high cumulative incidence of relapse (CIR) of 33% and 29.9%, respectively. Outcome was best for RCC patients with highest EFS (76.3%; 57.1% if IST failure was considered as event) and lowest CIR (9.3%). This study highlights that paediatric MDS and JMML are very rare disorders with associated morbidity and mortality, especially in high grade MDS and JMML. Considering the high relapse risk in high grade MDS and JMML, new therapeutic options are required.

(BELG J HEMATOL 2020;11(6):233-9)

Leukaemic stem cells in AML: where are we now? An update on recent findings and detection

SUMMARY

Ample evidence was provided these past decades that leukaemic stem cells (LSC) play a role in the outcome of adult and paediatric acute myeloid leukaemia (AML) patients. Although it is generally accepted that the CD34+/ CD38- compartment is most LSC-enriched, novel data have emerged illustrating a distinct biology between CD34+ and CD34- AML. In this review, we discuss the main LSC phenotypes in CD34+ and CD34- AML , as they are of utmost importance for the development of broadly applicable LSC-targeted strategies. The leukaemia-initiating capacity of these cells upon xenografting is still considered to be the gold standard for LSC detection. However, more feasible techniques have been researched to allow the implementation of LSC measurements into clinical practice. Here, we summarise the current state-of-the-art methodologies using flow cytometry and molecular detection, and emphasise their relevance in terms of prognosis and targeted drug therapy.

(BELG J HEMATOL 2020;11(6):246-52)

P.14.2 KIT D816 mutation in myeloid neoplasms: look out for systemic mastocytosis associated hematologic neoplasms (SM-AHN)

O.4 An in-depth investigation of the causes of treatment failure in AML

PP01 Exploring the long non-coding RNA landscape in Juvenile Myelomonocytic Leukemia