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  1. Article ; Online: A tower of babel of acronyms? The shadowlands of MGUS/MBL/CHIP/TCUS.

    Bravo-Perez, Carlos / Gurnari, Carmelo

    Seminars in hematology

    2024  Volume 61, Issue 1, Page(s) 43–50

    Abstract: With the advent of outperforming and massive laboratory tools, such as multiparameter flow cytometry and next-generation sequencing, hematopoietic cell clones with putative abnormalities for a variety of blood malignancies have been appreciated in ... ...

    Abstract With the advent of outperforming and massive laboratory tools, such as multiparameter flow cytometry and next-generation sequencing, hematopoietic cell clones with putative abnormalities for a variety of blood malignancies have been appreciated in otherwise healthy individuals. These conditions do not fulfill the criteria of their presumed cancer counterparts, and thus have been recognized as their precursor states. This is the case of monoclonal gammopathy of unknown significance (MGUS), the first blood premalignancy state described, preceding multiple myeloma (MM) or Waldenström macroglobulinemia (WM). However, in the last 2 decades, an increasing list of clonopathies has been recognized, including monoclonal B cell lymphocytosis (MBL), which antecedes chronic lymphocytic leukemia (CLL), clonal hematopoiesis of indeterminate potential (CHIP) for myeloid neoplasms (MN), and T-cell clones of uncertain significance (TCUS) for T-cell large chronic lymphocytic leukemia (LGLL). While for some of these entities diagnostic boundaries are precisely set, for others these are yet to be fully defined. Moreover, despite mostly considered of "uncertain significance," they have not only appeared to predispose to malignancy, but also to be capable of provoking set of immunological and cardiovascular complications that may require specialized management. The clinical implications of the aberrant clones, together with the extensive knowledge generated on the pathogenetic events driving their evolution, raises the question whether earlier interventions may alter the natural history of the disease. Herein, we review this Tower of Babel of acronyms pinpointing diagnostic definitions, differential diagnosis, and the role of genomic profiling of these precursor states, as well as potential interventional strategies.
    MeSH term(s) Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; B-Lymphocytes/pathology ; Lymphocytosis/diagnosis ; Lymphocytosis/pathology ; Clonal Hematopoiesis ; T-Lymphocytes/pathology ; Clone Cells/pathology
    Language English
    Publishing date 2024-01-19
    Publishing country United States
    Document type Review ; Journal Article
    ZDB-ID 206923-4
    ISSN 1532-8686 ; 0037-1963
    ISSN (online) 1532-8686
    ISSN 0037-1963
    DOI 10.1053/j.seminhematol.2024.01.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: From bone marrow failure syndromes to VEXAS: Disentangling clonal hematopoiesis, immune system, and molecular drivers.

    Gurnari, Carmelo / Visconte, Valeria

    Leukemia research

    2023  Volume 127, Page(s) 107038

    Abstract: Clonal hematopoiesis (CH) is a result of the selective expansion of hematopoietic stem and progenitor cells (HSPCs) carrying somatic mutations originating from a primary HSC. The advent of modern genomic technologies has helped recognizing that CH is ... ...

    Abstract Clonal hematopoiesis (CH) is a result of the selective expansion of hematopoietic stem and progenitor cells (HSPCs) carrying somatic mutations originating from a primary HSC. The advent of modern genomic technologies has helped recognizing that CH is common in elderly healthy subjects as a result of the aging bone marrow (BM). CH in healthy subjects without abnormalities in blood counts is known as CH of indeterminate potential. CH is also seen in BM failure (BMF) disorders. Whether CH alarms for the risk to develop malignant evolution in BMF or creates an adaptation to selective pressure is a matter of controversy. As such, a continuum might exist from pre-malignant to malignant hematopoietic diseases. This review summarizes how somatic mutations and immune derangement in HSCs shape disease evolution and describes the complexity of disorders such as VEXAS as the prototypic tetrad of somatic mutations, morphologic features, inflammatory pathways and immune overshooting. In such a view, we interconnect the axis aging and immune-hematopoietic system, which all convey important clues for the risk to develop malignancies.
    MeSH term(s) Humans ; Aged ; Clonal Hematopoiesis/genetics ; Hematopoiesis/genetics ; Bone Marrow ; Bone Marrow Failure Disorders ; Mutation
    Language English
    Publishing date 2023-02-11
    Publishing country England
    Document type Review ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 752396-8
    ISSN 1873-5835 ; 0145-2126
    ISSN (online) 1873-5835
    ISSN 0145-2126
    DOI 10.1016/j.leukres.2023.107038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Digging into the HLA pockets: A new association with acute leukaemias.

    Gurnari, Carmelo / Pagliuca, Simona

    British journal of haematology

    2022  Volume 200, Issue 2, Page(s) 123–125

    Abstract: Acute leukaemias represent a highly heterogeneous group of clonal proliferations of myeloid or lymphoid blasts. In the last decade, the contribution of immunogenetics to cancer biology has elicited a renewed interest in the structures of immune adaptive ... ...

    Abstract Acute leukaemias represent a highly heterogeneous group of clonal proliferations of myeloid or lymphoid blasts. In the last decade, the contribution of immunogenetics to cancer biology has elicited a renewed interest in the structures of immune adaptive responses, due to the growing body of evidence concerning their involvement into disease pathogenesis and treatment. The report by Boukouaci and colleagues suggests new associations between patterns of distribution of specific human leukocyte antigen motifs and leukaemogenesis. Commentary on Boukouaci Wahid et al. Comparative analysis of the variability of the HLA peptide-binding pockets in patients with acute leukemias" Br J Haematol 2023;200:203-215.
    MeSH term(s) Humans ; Leukemia/genetics ; Acute Disease ; Histocompatibility Antigens Class II ; HLA Antigens
    Chemical Substances Histocompatibility Antigens Class II ; HLA Antigens
    Language English
    Publishing date 2022-11-07
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.18529
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Clonal evolution in aplastic anemia: failed tumor surveillance or maladaptive recovery?

    Gurnari, Carmelo / Pagliuca, Simona / Maciejewski, Jaroslaw P

    Leukemia & lymphoma

    2023  Volume 64, Issue 8, Page(s) 1389–1399

    Abstract: Clonal evolution to secondary paroxysmal nocturnal hemoglobinuria (PNH) or myeloid neoplasia (MN) represents one of the long-term complications of patients with aplastic anemia (AA). The recent evidence in the field of immunology and the application of ... ...

    Abstract Clonal evolution to secondary paroxysmal nocturnal hemoglobinuria (PNH) or myeloid neoplasia (MN) represents one of the long-term complications of patients with aplastic anemia (AA). The recent evidence in the field of immunology and the application of next-generation sequencing have shed light on the molecular underpinnings of these clonal complications, revealing clinical and molecular risk factors as well as potential immunological players. Particularly, whether MN evolution represents a failed tumor surveillance or a maladaptive recovery is still a matter of controversy in the field of bone marrow failure syndromes. However, recent studies have explored the precise dynamics of the immune-molecular forces governing such processes over time, generating knowledge useful for potential early therapeutic strategies. In this review, we will discuss the immune pathophysiology of AA and the emergence of clonal hematopoiesis with regard to the adaptive and maladaptive mechanisms at the basis of secondary evolution trajectories operating under the immune pressure.
    MeSH term(s) Humans ; Anemia, Aplastic/complications ; Hemoglobinuria, Paroxysmal/genetics ; Neoplasms/complications ; Bone Marrow Failure Disorders/complications ; Clonal Evolution/genetics
    Language English
    Publishing date 2023-06-25
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1042374-6
    ISSN 1029-2403 ; 1042-8194
    ISSN (online) 1029-2403
    ISSN 1042-8194
    DOI 10.1080/10428194.2023.2215614
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: 'We cannot paint them all with the same brush': the need for a better definition of patients with myelodysplastic syndromes for clinical trial design.

    Gurnari, Carmelo / Visconte, Valeria

    British journal of haematology

    2021  Volume 196, Issue 2, Page(s) 268–269

    MeSH term(s) Clinical Trials as Topic ; Humans ; Myelodysplastic Syndromes/diagnosis ; Myelodysplastic Syndromes/drug therapy
    Language English
    Publishing date 2021-10-24
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.17909
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Have we reached a molecular era in myelodysplastic syndromes?

    Voso, Maria Teresa / Gurnari, Carmelo

    Hematology. American Society of Hematology. Education Program

    2021  Volume 2021, Issue 1, Page(s) 418–427

    Abstract: Myelodysplastic syndromes (MDS) are characterized by heterogeneous biological and clinical characteristics, leading to variable outcomes. The availability of sophisticated platforms of genome sequencing allowed the discovery of recurrently mutated genes, ...

    Abstract Myelodysplastic syndromes (MDS) are characterized by heterogeneous biological and clinical characteristics, leading to variable outcomes. The availability of sophisticated platforms of genome sequencing allowed the discovery of recurrently mutated genes, which have led to a new era in MDS. This is reflected by the 2016 update of the World Health Organization classification, in which the criteria to define MDS with ringed sideroblasts include the presence of SF3B1 mutations. Further, the detection of somatic mutations in myeloid genes at high variant allele frequency guides the diagnostic algorithm in cases with cytopenias, unclear dysplastic changes, and normal karyotypes, supporting MDS over alternative diagnoses. SF3B1 mutations have been shown to play a positive prognostic role, while mutations in ASXL1, EZH2, RUNX1, and TP53 have been associated with a dismal prognosis. This is particularly relevant in lower- and intermediate-risk disease, in which a higher number of mutations and/or the presence of "unfavorable" somatic mutations may support the use of disease-modifying treatments. In the near future, the incorporation of mutation profiles in currently used prognostication systems, also taking into consideration the classical patient clinical variables (including age and comorbidities), will support a more precise disease stratification, eg, the assignment to targeted treatment approaches or to allogeneic stem cell transplantation in younger patients.
    MeSH term(s) Aged ; Disease Management ; Female ; Gene Frequency ; Germ-Line Mutation ; Hematopoietic Stem Cell Transplantation ; Humans ; Mutation ; Myelodysplastic Syndromes/diagnosis ; Myelodysplastic Syndromes/genetics ; Myelodysplastic Syndromes/therapy ; Prognosis
    Language English
    Publishing date 2021-12-18
    Publishing country United States
    Document type Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2084287-9
    ISSN 1520-4383 ; 1520-4391
    ISSN (online) 1520-4383
    ISSN 1520-4391
    DOI 10.1182/hematology.2021000276
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: How I manage acquired pure red cell aplasia in adults.

    Gurnari, Carmelo / Maciejewski, Jaroslaw P

    Blood

    2021  Volume 137, Issue 15, Page(s) 2001–2009

    Abstract: Pure red cell aplasia (PRCA) is a rare hematological disorder with multiple etiologies. The multifaceted nature of this disease is emphasized by the variety of concomitant clinical features. Classic idiopathic presentation aside, prompt recognition of ... ...

    Abstract Pure red cell aplasia (PRCA) is a rare hematological disorder with multiple etiologies. The multifaceted nature of this disease is emphasized by the variety of concomitant clinical features. Classic idiopathic presentation aside, prompt recognition of pathogenetic clues is important because of their diagnostic and therapeutic implications. As a consequence, treatment of PRCA is diverse and strictly dependent on the presented clinical scenario. Here, we propose a series of clinical vignettes that showcase instructive representative situations derived from our routine clinical practice. Using these illustrative clinical cases, we review the diagnostic workup needed for a precise diagnosis and the currently available therapeutic options, discussing their applications in regard to the various PRCA-associated conditions and individual patients' characteristics. Finally, we propose a treatment algorithm that may offer guidance for personalized therapeutic recommendations.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Disease Management ; Female ; Humans ; Male ; Precision Medicine ; Red-Cell Aplasia, Pure/diagnosis ; Red-Cell Aplasia, Pure/therapy
    Language English
    Publishing date 2021-03-03
    Publishing country United States
    Document type Case Reports ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2021010898
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Aplastic anemia: Quo vadis?

    Gurnari, Carmelo / Maciejewski, Jaroslaw P

    Seminars in hematology

    2021  Volume 59, Issue 1, Page(s) 54–55

    Abstract: In the last 30 years, the field of aplastic anemia (AA), and more generally bone marrow failure syndromes, has undergone a multitude of new discoveries. The application of modern and sophisticated sequencing techniques unveiled a variety of genes ... ...

    Abstract In the last 30 years, the field of aplastic anemia (AA), and more generally bone marrow failure syndromes, has undergone a multitude of new discoveries. The application of modern and sophisticated sequencing techniques unveiled a variety of genes associated with these disorders and contributed to a better understanding of the disease pathobiology. This advancement was paralleled by the discovery, clinical testing and subsequent approval of new drugs for the treatment of AA and associated disorders. Several additional agents are currently under evaluation for possible therapies. Herein, we look at the potential future avenues of research in AA through a brief summary of an intergenerational Socratic dialogue between the mentor, who witnessed and actively contributed to the milestones achieved in the last 30 years, and his fellow, who would himself go on to become the mentor of a new generation of AA researchers.
    MeSH term(s) Anemia, Aplastic/drug therapy ; Anemia, Aplastic/genetics ; Bone Marrow Failure Disorders ; Humans
    Language English
    Publishing date 2021-12-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 206923-4
    ISSN 1532-8686 ; 0037-1963
    ISSN (online) 1532-8686
    ISSN 0037-1963
    DOI 10.1053/j.seminhematol.2021.12.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Copper Deficiency.

    Gurnari, Carmelo / Rogers, Heesun J

    The New England journal of medicine

    2021  Volume 385, Issue 7, Page(s) 640

    MeSH term(s) Aged ; Anemia/etiology ; Bone Marrow Cells/pathology ; Bone Marrow Examination ; Copper/deficiency ; Fatigue/etiology ; Female ; Humans ; Liver Function Tests
    Chemical Substances Copper (789U1901C5)
    Language English
    Publishing date 2021-08-07
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMicm2103532
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Diagnostic evaluation in bone marrow failure disorders: what have we learnt to help inform the transplant decision in 2024 and beyond?

    Ciangola, Giulia / Santinelli, Enrico / McLornan, Donal P / Pagliuca, Simona / Gurnari, Carmelo

    Bone marrow transplantation

    2024  Volume 59, Issue 4, Page(s) 444–450

    Abstract: Aplastic anemia (AA) is the prototypical bone marrow failure syndrome. In the current era of readily available 'molecular annotation', application of comprehensive next-generation sequencing panels has generated novel insights into underlying ... ...

    Abstract Aplastic anemia (AA) is the prototypical bone marrow failure syndrome. In the current era of readily available 'molecular annotation', application of comprehensive next-generation sequencing panels has generated novel insights into underlying pathogenetic mechanisms, potentially leading to improvements in personalized therapeutic approaches. New evidence has emerged as to the role of somatic loss of HLA class I allele expression in 'immune-mediated' AA, associated molecular aberrations, and risk of clonal evolution. A deeper understanding has emerged regarding the role of 'myeloid' gene mutations in this context, translating patho-mechanistic insights derived from wider clinical and translational research within the myeloid disorder arena. Here, we review contemporary 'tools' which aid in confirmation of a diagnosis of AA, with an additional focus on their potential in guiding therapeutic options. A specific emphasis is placed upon interpretation and integration of this detailed diagnostic information and how this may inform optimal transplantation strategies.
    MeSH term(s) Humans ; Anemia, Aplastic/diagnosis ; Anemia, Aplastic/genetics ; Anemia, Aplastic/therapy ; Bone Marrow Failure Disorders ; Mutation
    Language English
    Publishing date 2024-01-30
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 632854-4
    ISSN 1476-5365 ; 0268-3369 ; 0951-3078
    ISSN (online) 1476-5365
    ISSN 0268-3369 ; 0951-3078
    DOI 10.1038/s41409-024-02213-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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