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Triple-Negative Essential Thrombocythemia: Clinical-Pathological and Molecular Features. A Single-Center Cohort Study
- Source :
- Frontiers in Oncology, Vol 11 (2021), Frontiers in Oncology
- Publication Year :
- 2021
- Publisher :
- Frontiers Media S.A., 2021.
-
Abstract
- 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.
- Subjects :
- Cancer Research
medicine.medical_specialty
Pathology
Myeloid
lcsh:RC254-282
Myeloid Neoplasm
03 medical and health sciences
0302 clinical medicine
Internal medicine
Genotype
medicine
Myelofibrosis
Original Research
Hematology
triple-negative
Essential thrombocythemia
business.industry
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
bone marrow morphology
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Concomitant
next-generation sequencing
Bone marrow
prognosis
business
essential thrombocytemia
030215 immunology
Subjects
Details
- Language :
- English
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Frontiers in Oncology
- Accession number :
- edsair.doi.dedup.....4fc4b547fdd24aa03c46faf53ae07f6c
- Full Text :
- https://doi.org/10.3389/fonc.2021.637116/full