PNH clones prevalence study in ph-negative myeloproliferative neoplasms: a multicenter Italian study

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Paroxysmal nocturnal hemoglobinuria (PNH) clone prevalence is understudied in myeloproliferative neoplasms (MPN).
• MPN patients often present with anemia, elevated LDH, asthenia, and thrombosis.
• PNH clones are characterized by glycosyl-phosphatidyl-inositol (GPI)-deficient cells.

Purpose of the Study:

• To determine the prevalence of PNH clones in 119 Philadelphia chromosome-negative MPN patients.
• To investigate the clinical characteristics and genetic landscape of MPN patients with PNH clones.

Main Methods:

• Multicenter study involving standardized diagnostic testing for PNH clones in granulocytes, monocytes, and erythrocytes.
• Next-generation sequencing (NGS) was utilized for genetic analysis in selected PNH-positive and PNH-negative MPN cases.
• Clinical data including symptoms, thrombosis history, and splenomegaly were collected.

Main Results:

• PNH positive clones were detected in 3.23% (3 out of 119) of MPN patients.
• All three PNH-positive patients had splenomegaly; none had a history of thrombosis.
• PNH clones were associated with CALR or JAK2^V617F mutations, with PIGA deletion observed in PNH-positive cases.

Conclusions:

• The study suggests a potential association between CALR and JAK2^V617F mutations and the presence of PNH clones in MPN.
• The acquisition of multiple genetic mutations, including PNH clones, may indicate a worsening of the malignant process in MPN.
• Further research is warranted to elucidate the clinical implications and management strategies for MPN patients with PNH clones.