B. Maes MD, PhD

Case series of two patients with KIT D816V positive systemic mastocytosis with associated chronic myelomonocytic leukaemia

SUMMARY

In this case report, we describe two patients with systemic mastocytosis with an associated haematological neoplasm. The KIT c.2447A>T;p. (Asp816Val) (D816V) mutation, the original driver mutation of mastocytosis, can, in combination with additional genetic abnormalities, drive the clonal evolution towards an additional myelodysplastic or myeloproliferative neoplasia. When patients present with a dominant phenotype of the latter neoplasia, which is often the cause in chronic myelomonocytic leukaemia (CMML) or acute myeloid leukaemia (AML), the original mastocytosis could be overlooked, missing therapeutic opportunities.

(BELG J HEMATOL 2023;14(4):178–82)

Diagnostic testing in myeloid malignancies by next-generation sequencing: recommendations from the Commission Personalised Medicine

SUMMARY

Molecular diagnostics have an increasing impact on diagnosis, risk stratification and targeted treatment in haemato-oncology. In the framework of a pilot study for the implementation of next-generation sequencing in the Belgian healthcare system, the Commission of Personalised Medicine was founded to give professional and evidence-based advice on the molecular analysis in haemato-oncology. This paper describes its recommendations for NGS analysis in myeloid malignancies. In addition, the minimally required set of genes that must be analysed is defined and algorithms for molecular workflow in myeloid malignancies are proposed.

(BELG J HEMATOL 2019;10(6):241–9)

P57 Screening and follow-up for paroxysmal nocturnal hemoglobinuria

Diffuse large B-cell lymphoma presenting as a spontaneous rupture of the spleen

SUMMARY

In this hematocase, a patient is presented with a spontaneous rupture of the spleen due to massive splenomegaly caused by a previously undiagnosed diffuse large B-cell lymphoma. Diagnosis and differentiation of this non-Hodgkin lymphoma is discussed with attention for the prognostic implications of the results. The association between spontaneous rupture of the spleen and haematological malignancies is further explored by means of earlier described cases. A take home message is given regarding this rare initial presentation of a lymphoma since immediate surgical intervention is imperative in these cases.

(BELG J HEMATOL 2017;8(6):239–43)

PP33 Targeted next-generation sequencing using a pan-myeloid panel in myelodysplastic neoplasms: implementation in clinical diagnostics

Targeted next generation sequencing in myeloid neoplasms

Summary

For most haematological disease entities whole genome and/or exome sequencing efforts identified a core set of recurrently mutated genes. Multiplex DNA mutation screening proves to be highly applicable for myeloid malignancies, since mutations in many genes, e.g. FLT3, NPM1, CEBPA, KIT, DNMT3A, IDH1, IDH2, TET2, ASXL1, RUNX1, SF3B1, SRSF2, U2AF1, ZRSR2, TP53, STAG2, SMC1A, SMC3, RAD21, PHF6, RAS, EZH2, ETV6, JAK2, MPL, CALR, SETBP1, CSF3R, are described to be significantly associated with diagnosis, disease subtyping, prognostication, and/or for tailoring therapy. Obviously, their analysis is no longer feasible using conventional, single gene molecular diagnostic techniques, urging the use of a multi-gene ‘pan-myeloid’ Next Generation Sequencing panel.

(BELG J HEMATOL 2016; 7(3):98–102)

Challenges and pitfalls of next generation sequencing in molecular haematology

Summary

In the past few years the cost of next generation sequencing decreased substantially and the technology has significantly matured, allowing for its introduction into clinical practice. For most haematological disease entities whole genome and/or exome sequencing efforts identified a core set of recurrently mutated genes. Several of these genes are expected to be included in the upcoming revision of the 2008 edition of the World Health Organisation classification of haematological malignancies. Next generation sequencing technology allows transforming current single gene mutation analysis into multiplexed mutational profiling. Next generation ‘deep’ sequencing is a promising new tool to monitor minimal disease burden and to detect mutations within malignant subclones. With current platforms point mutations can be detected with a sensitivity of 1–5% mutant DNA. For indel mutations or clonal IG/TCR rearrangements sensitivity in the range of 10⁻⁵ can be reached. In this review we will highlight the opportunities and challenges of the introduction of next generation sequencing technology into a setting where it will contribute significantly to individual patient cancer management.

(BELG J HEMATOL 2016;7(2):63–8)