413 results found
Chen X, Wang W, Yeh J, et al., 2023, Clinical Validation of FusionPlex RNA Sequencing and Its Utility in the Diagnosis and Classification of Hematologic Neoplasms., J Mol Diagn, Vol: 25, Pages: 932-944
Recurrent gene rearrangements result in gene fusions that encode chimeric proteins, driving the pathogenesis of many hematologic neoplasms. The fifth edition World Health Organization classification and International Consensus Classification 2022 include an expanding list of entities defined by such gene rearrangements. Therefore, sensitive and rapid methods are needed to identify a broad range of gene fusions for precise diagnosis and prognostication. In this study, we validated the FusionPlex Pan-Heme panel analysis using anchored multiplex PCR/targeted RNA next-generation sequencing for routine clinical testing. Furthermore, we assessed its utility in detecting gene fusions in myeloid and lymphoid neoplasms. The validation cohort of 61 cases demonstrated good concordance between the FusionPlex Pan-Heme panel and other methods, including chromosome analysis, fluorescence in situ hybridization, RT-PCR, and Sanger sequencing, with an analytic sensitivity and specificity of 95% and 100%, respectively. In an independent cohort of 28 patients indicated for FusionPlex testing, gene fusions were detected in 21 patients. The FusionPlex Pan-Heme panel analysis reliably detected fusion partners and patient-specific fusion sequences, allowing accurate classification of hematologic neoplasms and the discovery of new fusion partners, contributing to a better understanding of the pathogenesis of the diseases.
Zayac AS, Landsburg DJ, Hughes ME, et al., 2023, High-grade B-cell lymphoma, not otherwise specified: a multi-institutional retrospective study., Blood Adv, Vol: 7, Pages: 6381-6394
In this multi-institutional retrospective study, we examined the characteristics and outcomes of 160 patients with high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS)-a rare category defined by high-grade morphologic features and lack of MYC rearrangements with BCL2 and/or BCL6 rearrangements ("double hit"). Our results show that HGBL-NOS tumors are heterogeneous: 83% of patients had a germinal center B-cell immunophenotype, 37% a dual-expressor immunophenotype (MYC and BCL2 expression), 28% MYC rearrangement, 13% BCL2 rearrangement, and 11% BCL6 rearrangement. Most patients presented with stage IV disease, a high serum lactate dehydrogenase, and other high-risk clinical factors. Most frequent first-line regimens included dose-adjusted cyclophosphamide, doxorubicin, vincristine, and etoposide, with rituximab and prednisone (DA-EPOCH-R; 43%); rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 33%); or other intensive chemotherapy programs. We found no significant differences in the rates of complete response (CR), progression-free survival (PFS), or overall survival (OS) between these chemotherapy regimens. CR was attained by 69% of patients. PFS at 2 years was 55.2% and OS was 68.1%. In a multivariable model, the main prognostic factors for PFS and OS were poor performance status, lactate dehydrogenase >3 × upper limit of normal, and a dual-expressor immunophenotype. Age >60 years or presence of MYC rearrangement were not prognostic, but patients with TP53 alterations had a dismal PFS. Presence of MYC rearrangement was not predictive of better PFS in patients treated with DA-EPOCH-R vs R-CHOP. Improvements in the diagnostic criteria and therapeutic approaches beyond dose-intense chemotherapy are needed to overcome the unfavorable prognosis of patients with HGBL-NOS.
Tan L, Bansal G, Yeung CC, et al., 2023, Leukemic non-nodal cyclin D1- and SOX11-negative mantle cell lymphoma with CCND3::IGH rearrangement., Ann Hematol
Yeung CCS, Woolston DW, Wu V, et al., 2023, Abnormal bone marrow findings in patients following treatment with chimeric antigen receptor-T cell therapy, EUROPEAN JOURNAL OF HAEMATOLOGY, ISSN: 0902-4441
Alaggio R, Amador C, Anagnostopoulos I, et al., 2023, The 5th edition of The World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms (vol 36, pg 1720, 2022), LEUKEMIA, ISSN: 0887-6924
Torabi A, Naresh KN, 2023, T-cell prolymphocytic leukemia/lymphoma with <i>TCRB::TCL1</i> translocation, BLOOD, Vol: 142, Pages: 119-119, ISSN: 0006-4971
Fromm JR, Tang C, Naresh KN, 2023, Predictors of risk of relapse in classic Hodgkin lymphoma, JOURNAL OF CLINICAL PATHOLOGY, Vol: 76, Pages: 414-417, ISSN: 0021-9746
Torabi A, Fromm JR, Naresh KN, 2023, MEF2B is the ideal immunohistochemical marker to highlight neoplastic LP cells in nodular lymphocyte-predominant Hodgkin lymphoma., EJHaem, Vol: 4, Pages: 517-519
El-Sharkawi D, Sud A, Prodger C, et al., 2023, A retrospective study of MYC rearranged diffuse large B-cell lymphoma in the context of the new WHO and ICC classifications, Blood Cancer Journal, Vol: 13, ISSN: 2044-5385
Chen K, Hendrie PCC, Naresh KNN, 2023, Aleukemic mast cell leukemia, well-differentiated and chronic type, ANNALS OF HEMATOLOGY, ISSN: 0939-5555
Siebert R, Schuh A, Ott G, et al., 2023, Response to the Comments from the Groupe Francophone de Cytogenetique Hematologique (GFCH) on the 5th edition of the World Health Organization classification of haematolymphoid tumors, LEUKEMIA, ISSN: 0887-6924
Bewicke-Copley F, Korfi K, Araf S, et al., 2023, Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type diffuse large B-cell lymphoma, BLOOD ADVANCES, Vol: 7, Pages: 845-855, ISSN: 2473-9529
Stacey A, Marks AJ, Naresh KN, 2023, Variant histology in nodular lymphocyte predominant Hodgkin lymphoma in an adult population: disease investigations and characteristics from a retrospective cohort, JOURNAL OF CLINICAL PATHOLOGY, Vol: 76, Pages: 137-140, ISSN: 0021-9746
Naik A, Gooley T, Loeb K, et al., 2022, The impact of histological grade on outcomes in follicular lymphoma: An analysis of patients in the SEER database in the context of evolving disease classification and treatment, BRITISH JOURNAL OF HAEMATOLOGY, Vol: 199, Pages: 696-706, ISSN: 0007-1048
Pai SA, Naresh KN, Borges AM, 2022, Report of a Case With Clinical and Pathologic Features of Castleman Disease That Predates Castleman's Report by More Than 50 Years, ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE, Vol: 146, Pages: 1412-1415, ISSN: 0003-9985
Naresh KN, 2022, Proposal of 'reactive-lymphocyte/histiocyte rich large B-cell lymphoma' as an alternate term for 'nodular lymphocyte predominant Hodgkin lymphoma' that would also address its overlap with T-cell/histiocyte rich large B-cell lymphoma., EJHaem, Vol: 3, Pages: 1449-1451
Ju JY, Sorensen EP, Walsh JS, et al., 2022, CD5<SUP>+</SUP> Gamma Delta T-Cell Lymphoproliferative Disorder/Lymphoma Without Cytotoxic Granules in the Skin, AMERICAN JOURNAL OF DERMATOPATHOLOGY, Vol: 44, Pages: 680-682, ISSN: 0193-1091
Alaggio R, Amador C, Anagnostopoulos I, et al., 2022, The 5th edition of the World Health Organization classification of haematolymphoid tumours: lymphoid neoplasms, Leukemia, Vol: 36, Pages: 1720-1748, ISSN: 0887-6924
We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.
Khoury JD, Solary E, Abla O, et al., 2022, The 5th edition of the World Health Organization classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms, Leukemia, Vol: 36, Pages: 1703-1719, ISSN: 0887-6924
The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.
Attygalle AD, Dobson R, Chak PK, et al., 2022, Parallel evolution of two distinct lymphoid proliferations in clonal haematopoiesis, HISTOPATHOLOGY, Vol: 80, Pages: 847-858, ISSN: 0309-0167
Trasanidis N, Katsarou A, Ponnusamy K, et al., 2022, Systems medicine dissection of chr1q-amp reveals a novel PBX1-FOXM1 axis for targeted therapy in multiple myeloma, BLOOD, Vol: 139, Pages: 1939-1953, ISSN: 0006-4971
Naresh KN, Lazzi S, Santi R, et al., 2022, A refined approach to the diagnosis of Burkitt lymphoma in a resource-poor setting, HISTOPATHOLOGY, Vol: 80, Pages: 743-745, ISSN: 0309-0167
Ponnusamy K, Tzioni MM, Begum M, et al., 2022, The innate sensor ZBP1-IRF3 axis regulates cell proliferation in multiple myeloma, HAEMATOLOGICA, Vol: 107, Pages: 721-732, ISSN: 0390-6078
Ibanez K, Polke J, Hagelstrom RT, et al., 2022, Whole genome sequencing for the diagnosis of neurological repeat expansion disorders in the UK: a retrospective diagnostic accuracy and prospective clinical validation study, LANCET NEUROLOGY, Vol: 21, Pages: 234-245, ISSN: 1474-4422
Chen X, Fromm JR, Naresh KN, 2022, "Blasts" in myeloid neoplasms - how do we define blasts and how do we incorporate them into diagnostic schema moving forward?, LEUKEMIA, Vol: 36, Pages: 327-332, ISSN: 0887-6924
Trasanidis N, Katsarou A, Ponnusamy K, et al., 2021, Systems medicine dissection of chromosome 1q amplification reveals oncogenic regulatory circuits and informs targeted therapy in cancer
<jats:title>Abstract</jats:title><jats:p>Understanding the biological and clinical impact of copy number aberrations (CNA) in cancer remains an unmet challenge. Genetic amplification of chromosome 1q (chr1q-amp) is a major CNA conferring adverse prognosis in several cancers, including the blood cancer, multiple myeloma (MM). Although several chr1q genes portend high-risk MM disease, the underpinning molecular aetiology remains elusive. Here we integrate patient multi-omics datasets with genetic variables to identify 103 adverse prognosis genes in chr1q-amp MM. Amongst these, the transcription factor PBX1 is ectopically expressed by genetic amplification and epigenetic activation of its own preserved 3D regulatory domain. By binding to reprogrammed super-enhancers, PBX1 directly regulates critical oncogenic pathways, whilst in co-operation with FOXM1, activates a proliferative gene signature which predicts adverse prognosis across multiple cancers. Notably, pharmacological disruption of the PBX1-FOXM1 axis, including with a novel PBX1 inhibitor is selectively toxic against chr1q-amp cancer cells. Overall, our systems medicine approach successfully identifies CNA-driven oncogenic circuitries, links them to clinical phenotypes and proposes novel CNA-targeted therapy strategies in cancer.</jats:p><jats:sec><jats:title>Significance</jats:title><jats:p>We provide a comprehensive systems medicine strategy to unveil oncogenic circuitries and inform novel precision therapy decisions against CNA in cancer. This first clinical multi-omic analysis of chr1q-amp in MM identifies a central PBX1-FOXM1 regulatory axis driving high-risk prognosis, as a novel therapeutic target against chr1q-amp in cancer.</jats:p></jats:sec>
Smedley D, Smith KR, Martin A, et al., 2021, 100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care - Preliminary Report, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 385, Pages: 1868-1880, ISSN: 0028-4793
Medani H, Elshiekh M, Naresh KN, 2021, Improving precise counting of mitotic cells in mantle cell lymphoma using phosphohistone H3 (PHH3) antibody, JOURNAL OF CLINICAL PATHOLOGY, Vol: 74, Pages: 646-649, ISSN: 0021-9746
Claudiani S, Mason CC, Milojkovic D, et al., 2021, Carfilzomib Enhances the Suppressive Effect of Ruxolitinib in Myelofibrosis, CANCERS, Vol: 13
Xu D, Naresh KN, 2021, Leukemic presentation of a highly aggressive ALK-negative anaplastic large cell lymphoma, BLOOD, Vol: 138, Pages: 1198-1198, ISSN: 0006-4971
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