Hairy Cell Leukaemia

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• Hairy cell leukaemia (HCL) is a rare B-cell malignancy with two main subtypes: classical (HCLc) and variant (HCLv).
• Understanding the molecular pathogenesis is crucial for diagnosis and treatment strategies.

Purpose of the Study:

• To review diagnostic findings differentiating HCLc and HCLv.
• To discuss prognosis and current treatment indications, including novel therapies.
• To link therapeutic approaches with molecular pathogenesis insights.

Main Methods:

• Review of diagnostic clinical and laboratory findings.
• Analysis of current treatment strategies and novel therapies.
• Correlation of treatment outcomes with molecular pathogenesis, including BRAF V600E mutations.

Main Results:

• HCLc is frequently associated with the BRAF V600E mutation, activating the MEK/ERK pathway.
• Purine nucleoside analogue (PNA) therapy, often with rituximab, is the standard for HCLc, improving response and MRD clearance.
• Novel targeted therapies like BRAF inhibitors, moxetumomab, and BTK inhibitors are emerging for relapsed/refractory HCLc.
• HCLv has a poorer prognosis, and while PNA/rituximab improves response, novel agents like moxetumomab or ibrutinib have limited evidence.

Conclusions:

• The BRAF V600E mutation is a key driver in HCLc, guiding targeted therapy development.
• While PNA-based regimens are effective, understanding relapse and refractoriness necessitates exploring novel agents.
• HCLv management remains challenging, requiring further research into effective treatment modalities.