Myelodysplastic neoplasms (MDS) are clonal hematopoietic neoplasms. Chromosomal abnormalities (CAs) are detected in 40-45% of de novo MDS and up to 80% of post-cytotoxic therapy MDS (MDS-pCT). Lately, several changes appeared in World Health Organization (WHO) classification and International Consensus Classification (ICC). The novel \'biallelic TP53 inactivation\' (also called \'multi-hit TP53\') MDS entity requires systematic investigation of TP53 locus (17p13.1). The ICC maintains CA allowing the diagnosis of MDS without dysplasia (del(5q), del(7q), -7 and complex karyotype). Deletion 5q is the only CA, still representing a low blast class of its own, if isolated or associated with one additional CA other than -7 or del(7q) and without multi-hit TP53. It represents one of the most frequent aberrations in adults\' MDS, with chromosome 7 aberrations, and trisomy 8. Conversely, translocations are rarer in MDS. In children, del(5q) is very rare while -7 and del(7q) are predominant. Identification of a germline predisposition is key in childhood MDS. Aberrations of chromosomes 5, 7 and 17 are the most frequent in MDS-pCT, grouped in complex karyotypes. Despite the ever-increasing importance of molecular features, cytogenetics remains a major part of diagnosis and prognosis. In 2022, a molecular international prognostic score (IPSS-M) was proposed, combining the prognostic value of mutated genes to the previous scoring parameters (IPSS-R) including cytogenetics, still essential. A karyotype on bone marrow remains mandatory at diagnosis of MDS with complementary molecular analyses now required. Analyses with FISH or other technologies providing similar information can be necessary to complete and help in case of karyotype failure, for doubtful CA, for clonality assessment, and for detection of TP53 deletion to assess TP53 biallelic alterations.

Cytogenetic analysis is mandatory at initial assessment of B-cell acute lymphoblastic leukemia (B-ALL) due to its diagnostic and prognostic value. Results from chromosome banding analysis and complementary FISH are taken into account in therapeutic protocols and further completed by other techniques (RT-PCR, SNP-array, MLPA, NGS, OGM). Indeed, new genomic entities have been identified by NGS, mostly RNA sequencing, such as Ph-like ALL that can benefit from targeted therapy. Here, we have attempted to establish cytogenetic guidelines by reviewing the most recent published data including the novel 5th World Health Organization and International Consensus Classifications. We also focused on newly described cytogenomic entities and indicate alternative diagnostic tools such as NGS technology, as its importance is vastly increasing in the diagnostic setting.

Chromosomal abnormalities are frequent in chronic lymphocytic leukemia (CLL), and most have prognostic value. In addition to the four well-known abnormalities (13q, 11q and 17p deletions, and trisomy 12), other recurrent aberrations have been linked to the disease outcome and/or drug resistance. Moreover, the complex karyotype has recently emerged as a prognostic marker for patients undergoing immunochemotherapy or targeted therapies. Here, we describe the main chromosomal abnormalities identified in CLL and related disorders (small lymphocytic lymphoma and monoclonal B-cell lymphocytosis) by reviewing the most recent literature and discussing their detection and clinical impact. Lastly, we provide technical guidelines and a strategy for the cytogenetic assessment of CLL.

Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells (PCs) in the bone marrow. Despite considerable advances in the treatment, MM is considered an incurable chronic disease with a very heterogeneous prognosis, mostly depending on genomic alterations whose complexity evolves over time. The cytogenetic analysis of MM is performed on CD138+ sorted PCs, in order to detect the following high risk cytogenetic abnormalities: t(4;14), 17p/TP53 deletion, 1q21 gain/amplification, 1p32 deletion, as well as t(11;14) because of its therapeutic implication. This minimal panel can be enlarged to detect other recurrent abnormalities, according to the prognostic score chosen by the laboratory. Although the knowledge of the genetic landscape of MM is evolving rapidly with improved molecular technologies, risk scores remain to be refined as they require more time for consensual validation. The GFCH present here the overview of genomics alterations identified in MM and related PCs diseases associated with their prognostic factor, when available, and recommendations from an expert group for identification and characterization of those alterations. This work is the update of previous 2016 recommendations.

Acquired clonal chromosomal abnormalities (CAs) are usually considered to be disease-related. However, when a CA of this type is the only abnormality present (and especially in small clones), the clinical significance is unclear. Here, we review the literature on recurrent CAs whose significance is regularly subject to debate. Our objective was to help with their interpretation and develop guidelines for sex chromosome loss, trisomy 15, trisomy 8, deletion 20q and other isolated non-myelodysplastic neoplasm (MDS)-defining CAs. We suggest that non-MDS-defining CAs correspond to clonal hematopoiesis of indeterminate potential (CHIP) in the absence of cytopenia and clonal cytopenia of undetermined significance (CCUS) in the presence of cytopenia. Lastly, we review the literature on persistent polyclonal binucleated B-cell lymphocytosis; although usually benign, this condition may correspond to a premalignant state.

Bone marrow failure syndromes are rare disorders characterized by bone marrow hypocellularity and resultant peripheral cytopenias. The most frequent form is acquired, so-called aplastic anemia or idiopathic aplastic anemia, an auto-immune disorder frequently associated with paroxysmal nocturnal hemoglobinuria, whereas inherited bone marrow failure syndromes are related to pathogenic germline variants. Among newly identified germline variants, GATA2 deficiency and SAMD9/9L syndromes have a special significance. Other germline variants impacting biological processes, such as DNA repair, telomere biology, and ribosome biogenesis, may cause major syndromes including Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome. Bone marrow failure syndromes are at risk of secondary progression towards myeloid neoplasms in the form of myelodysplastic neoplasms or acute myeloid leukemia. Acquired clonal cytogenetic abnormalities may be present before or at the onset of progression; some have prognostic value and/or represent somatic rescue mechanisms in inherited syndromes. On the other hand, the differential diagnosis between aplastic anemia and hypoplastic myelodysplastic neoplasm remains challenging. Here we discuss the value of cytogenetic abnormalities in bone marrow failure syndromes and propose recommendations for cytogenetic diagnosis and follow-up.

Mature T-cell and natural killer (NK)-cell neoplasms (MTNKNs) are a highly heterogeneous group of lymphomas that represent 10-15 % of lymphoid neoplasms and have usually an aggressive behavior. Diagnosis can be challenging due to their overlapping clinical, histological and immunophenotypic features. Genetic data are not a routine component of the diagnostic algorithm for most MTNKNs. Indeed, unlike B-cell lymphomas, the genomic landscape of MTNKNs is not fully understood. Only few characteristic rearrangements can be easily identified with conventional cytogenetic methods and are an integral part of the diagnostic criteria, for instance the t(14;14)/inv(14) or t(X;14) abnormality harbored by 95 % of patients with T-cell prolymphocytic leukemia, or the ALK gene translocation observed in some forms of anaplastic large cell lymphoma. However, advances in molecular and cytogenetic techniques have brought new insights into MTNKN pathogenesis. Several recurrent genetic alterations have been identified, such as chromosomal losses involving tumor suppressor genes (SETD2, CDKN2A, TP53) and gains involving oncogenes (MYC), activating mutations in signaling pathways (JAK-STAT, RAS), and epigenetic dysregulation, that have improved our understanding of these pathologies. This work provides an overview of the cytogenetics knowledge in MTNKNs in the context of the new World Health Organization classification and the International Consensus Classification of hematolymphoid tumors. It describes key genetic alterations and their clinical implications. It also proposes recommendations on cytogenetic methods for MTNKN diagnosis.

Non-Hodgkin lymphomas (NHL) consist of a wide range of clinically, phenotypically and genetically distinct neoplasms. The accurate diagnosis of mature B-cell non-Hodgkin lymphoma relies on a multidisciplinary approach that integrates morphological, phenotypical and genetic characteristics together with clinical features. Cytogenetic analyses remain an essential part of the diagnostic workup for mature B-cell lymphomas. Karyotyping is particularly useful to identify hallmark translocations, typical cytogenetic signatures as well as complex karyotypes, all bringing valuable diagnostic and/or prognostic information. Besides the well-known recurrent chromosomal abnormalities such as, for example, t(14;18)(q32;q21)/IGH::BCL2 in follicular lymphoma, recent evidences support a prognostic significance of complex karyotype in mantle cell lymphoma and Waldenström macroglobulinemia. Fluorescence In Situ Hybridization is also a key analysis playing a central role in disease identification, especially in genetically-defined entities, but also in predicting transformation risk or prognostication. This can be exemplified by the pivotal role of MYC, BCL2 and/or BCL6 rearrangements in the diagnostic of aggressive or large B-cell lymphomas. This work relies on the World Health Organization and the International Consensus Classification of hematolymphoid tumors together with the recent cytogenetic advances. Here, we review the various chromosomal abnormalities that delineate well-established mature B-cell non-Hodgkin lymphoma entities as well as newly recognized genetic subtypes and provide cytogenetic guidelines for the diagnostic management of mature B-cell lymphomas.

Genetic data are becoming increasingly essential in the management of hematological neoplasms as shown by two classifications published in 2022: the 5th edition of the World Health Organization Classification of Hematolymphoid Tumours and the International Consensus Classification of Myeloid Neoplasms and Acute Leukemias. Genetic data are particularly important for acute myeloid leukemias (AMLs) because their boundaries with myelodysplastic neoplasms seem to be gradually blurring. The first objective of this review is to present the latest updates on the most common cytogenetic abnormalities in AMLs while highlighting the pitfalls and difficulties that can be encountered in the event of cryptic or difficult-to-detect karyotype abnormalities. The second objective is to enhance the role of cytogenetics among all the new technologies available in 2023 for the diagnosis and management of AML.

Molecular analysis is the hallmark of T-cell acute lymphoblastic leukemia (T-ALL) categorization. Several T-ALL sub-groups are well recognized based on the aberrant expression of specific transcription factors. This recently resulted in the implementation of eight provisional T-ALL entities into the novel 2022 International Consensus Classification, albeit not into the updated World Health Organization classification system. Despite this extensive molecular characterization, cytogenetic analysis remains the backbone of T-ALL diagnosis in many countries as chromosome banding analysis and fluorescence in situ hybridization are relatively inexpensive techniques to obtain results of diagnostic, prognostic and therapeutic interest. Here, we provide an overview of recurrent chromosomal abnormalities detectable in T-ALL patients and propose guidelines regarding their detection. By referring in parallel to the more general molecular classification approach, we hope to offer a diagnostic framework useful in a broad clinical genetic setting.