Genetic studies in clonal haematopoiesis, myelodysplastic neoplasms and acute myeloid leukaemia - a practical guide to WHO-HAEM5.

In recent years, technology developments and increase in knowledge have led to profound changes in the diagnostics of haematologic neoplasms, particularly myeloid neoplasms. Therefore an updated, fifth edition of the World Health Organization (WHO) classification of haematolymphoid neoplasms (WHO-HAEM5) will be issued in 2024. In this context, we present a practical guide for analysing the genetic aspects of clonal haematopoiesis of indeterminate potential (CHIP), clonal cytopenia of undetermined significance (CCUS), myelodysplastic neoplasms (MDS), and acute myeloid leukaemia (AML) based on WHO-HAEM5. This guide navigates through the genetic abnormalities underlying myeloid neoplasms which are required to be detected for classification according to WHO-HAEM5 and provides diagnostic algorithms.

Overview on WHO-HAEM5 and the diagnostic relevance of genetic alterations for the classification.

The landscape of haematological malignancies is constantly evolving, driven by advances in our understanding of their genetic basis. This has cumulated within the 5th Edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours published in short form in 2022 [1, 2] and being available in full length both as "Blue Book" (in print expected early 2024) as well as web-based classification (see: https://tumourclassification.iarc.who.int/welcome/). Similarly, the importance of genetic alterations for the classification is highlighted in other classification systems related to haematologic neoplasms [3-5]. In this special issue of the Medizinische Genetik, we present a comprehensive overview of the genetic alterations contributing to the classification of haematolymphoid neoplasms in the 5th Edition of the WHO classification (WHO-HAEM5) and its diagnostic relevance in the context of various haematological malignancies.

Genetic alterations in myeloproliferative and myelodysplastic/myeloproliferative neoplasms - a practical guide to WHO-HAEM5.

Within the World Health Organization (WHO) classification of haematopoietic neoplasms, particularly its fifth version from 2022 (WHO-HAEM5), myeloid neoplasms are not only grouped into myeloproliferative (MPN) and myelodysplastic neoplasms (MDS). There is also a group of haematological disorders that share features of both categories termed myelodysplastic /myeloproliferative neoplasms (MDS/MPN). In this article, we aim to provide a comprehensive and practical guide to WHO-HAEM5 highlighting the genetic alterations that underlie MPN and MDS/MPN. This guide provides an overview of the overlapping commonalities among these entities, as well as their unique characteristics.