Question

Discuss the diagnosis and prognosis of triple-negative myelofibrosis (TN-MF).

Hint:

TN-MF is diagnosed by the absence of JAK2, CALR, and MPL mutations, with prognosis being worse due to the aggressive nature of the disease.

Answer 1

Step 1: Diagnosis of Triple-Negative Myelofibrosis (TN-MF).
Triple-negative myelofibrosis (TN-MF) is a subtype of primary myelofibrosis characterized by the absence of mutations in the commonly associated genes (JAK2, CALR, and MPL). This condition is diagnosed based on: 1. Clinical features: Symptoms of TN-MF often include fatigue, weight loss, splenomegaly, and systemic inflammatory signs.
2. Bone marrow biopsy: A key diagnostic tool, which shows hypercellularity, increased reticulin fibrosis, and dysplastic features in hematopoietic cells. However, the absence of JAK2, CALR, or MPL mutations is crucial for confirming TN-MF.
3. Cytogenetic and molecular testing: Although TN-MF lacks these mutations, additional genetic abnormalities may be identified using next-generation sequencing or cytogenetic analysis.

Step 2: Prognosis of TN-MF.
The prognosis of TN-MF is generally poor compared to other subtypes of myelofibrosis. It tends to have a more aggressive course, with higher rates of progression to acute myeloid leukemia (AML) and shorter overall survival. Risk factors that contribute to prognosis include: 1. Fibrosis stage: More advanced fibrosis in the bone marrow correlates with a worse prognosis.
2. Age and comorbidities: Older age and the presence of comorbidities such as cardiovascular disease worsen prognosis.
3. Mutational burden: Though TN-MF lacks the common mutations, other mutations detected in genetic screening, such as ASXL1 or EZH2, can influence prognosis.