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Genomic profile of a patient with triple negative essential thrombocythemia, unresponsive to therapy: A case report and literature review.

ABSTRACT: Clonal analysis of patients with triple negative myeloproliferative neoplasm (MPN) has provided evidence of additional aberrations, including epigenetic alterations. To discover such novel genetic aberrations, patients were screened through next-generation sequencing using a myeloid sequencing panel of 54 genes using a genetic analyser. Genetic variants in 28 genes, including TET2, BCOR, BCR, and ABL1 were identified in a triple negative essential thrombocythemia (ET) patient. The individual role of some of these variants in disease pathogenesis has yet to be studied. Somatic mutations in the same genes have been reported with variable frequencies in myeloid malignancies. However, no pathogenic impact of these variants could be found; therefore, long-term follow up of patients with genetic analysis of a large cohort and the use of whole genome sequencing is required to assess the effects of these variants.

SUBMITTER: Zaidi U

PROVIDER: S-EPMC5435578 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Genomic profile of a patient with triple negative essential thrombocythemia, unresponsive to therapy: A case report and literature review.

Zaidi Uzma U Shahid Saba S Fatima Naveen N Ahmed Shariq S Sufaida Gul G Nadeem Muhammad M Shamsi Tahir T

Journal of advanced research 20170419 4

Clonal analysis of patients with triple negative myeloproliferative neoplasm (MPN) has provided evidence of additional aberrations, including epigenetic alterations. To discover such novel genetic aberrations, patients were screened through next-generation sequencing using a myeloid sequencing panel of 54 genes using a genetic analyser. Genetic variants in 28 genes, including <i>TET2, BCOR, BCR</i>, and <i>ABL1</i> were identified in a triple negative essential thrombocythemia (ET) patient. The ...[more]

PMID: 28560052

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Project description:Lack of demonstrable mutations affecting JAK2, CALR, or MPL driver genes within the spectrum of BCR-ABL1-negative myeloproliferative neoplasms (MPNs) is currently referred to as a triple-negative genotype, which is found in about 10% of patients with essential thrombocythemia (ET) and 5-10% of those with primary myelofibrosis (PMF). Very few papers are presently available on triple-negative ET, which is basically described as an indolent disease, differently from triple-negative PMF, which is an aggressive myeloid neoplasm, with a significantly higher risk of leukemic evolution. The aim of the present study was to evaluate the bone marrow morphology and the clinical-laboratory parameters of triple-negative ET patients, as well as to determine their molecular profile using next-generation sequencing (NGS) to identify any potential clonal biomarkers. We evaluated a single-center series of 40 triple-negative ET patients, diagnosed according to the 2017 WHO classification criteria and regularly followed up at the Hematology Unit of our Institution, between January 1983 and January 2019. In all patients, NGS was performed using the Illumina Ampliseq Myeloid Panel; morphological and immunohistochemical features of the bone marrow trephine biopsies were also thoroughly reviewed. Nucleotide variants were detected in 35 out of 40 patients. In detail, 29 subjects harbored one or two variants and six cases showed three or more concomitant nucleotide changes. The most frequent sequence variants involved the TET2 gene (55.0%), followed by KIT (27.5%). Histologically, most of the cases displayed a classical ET morphology. Interestingly, prevalent megakaryocytes morphology was more frequently polymorphic with a mixture of giant megakaryocytes with hyperlobulated nuclei, normal and small sized maturing elements, and naked nuclei. Finally, in five cases a mild degree of reticulin fibrosis (MF-1) was evident together with an increase in the micro-vessel density. By means of NGS we were able to identify nucleotide variants in most cases, thus we suggest that a sizeable proportion of triple-negative ET patients do have a clonal disease. In analogy with driver genes-mutated MPNs, these observations may prevent issues arising concerning triple-negative ET treatment, especially when a cytoreductive therapy may be warranted.

Dataset Information

Genomic profile of a patient with triple negative essential thrombocythemia, unresponsive to therapy: A case report and literature review.

Publications

Genomic profile of a patient with triple negative essential thrombocythemia, unresponsive to therapy: A case report and literature review.

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