Mutational profiling in suspected triple-negative essential thrombocythaemia using targeted next-generation...

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Essential thrombocythaemia (ET) is a myeloproliferative neoplasm primarily driven by mutations in JAK2, CALR, and MPL genes.
• A subset of ET patients, termed triple-negative ET (TN-ET), lack these common driver mutations.
• Accurate diagnosis of TN-ET can be challenging in real-world settings due to reliance on bone marrow examination.

Purpose of the Study:

• To investigate the genetic landscape of patients with suspected triple-negative ET using advanced sequencing techniques.
• To evaluate the necessity of repeat screening for driver mutations in ET.
• To assess the presence of clonality in suspected TN-ET cases.

Main Methods:

• A real-world cohort of 35 patients with suspected TN-ET underwent repeat screening for JAK2, CALR, and MPL mutations.
• Targeted next-generation sequencing (NGS) was employed to identify additional mutations.
• Patient data including age, platelet count, and thrombosis history were analyzed.

Main Results:

• Repeat screening identified driver mutations in 8 out of 35 patients (6 JAK2V617F, 2 CALR positive).
• NGS analysis revealed no mutations in 24 of 27 patients, with only three patients harboring other mutations.
• The majority of suspected TN-ET cases showed no evidence of clonality via targeted NGS.

Conclusions:

• Repeat screening for JAK2, CALR, and MPL mutations is crucial in suspected TN-ET cases.
• Targeted NGS analysis provides valuable insights into the genetic basis of ET.
• The diagnosis of TN-ET should be reconsidered in the absence of a detectable clonal marker.