Evaluation of "increased" hemoglobin in the JAK2 mutations era: a diagnostic algorithm based on genetic tests

Area of Science:

• Hematology
• Molecular Genetics
• Clinical Diagnostics

Background:

• Polycythemia vera (PV) and congenital polycythemia (CP) are distinct conditions characterized by an excess of red blood cells.
• Understanding the molecular underpinnings of these disorders is crucial for accurate diagnosis and management.
• Recent advances highlight specific genetic mutations associated with PV and CP.

Purpose of the Study:

• To outline the current diagnostic approaches for polycythemia based on molecular pathogenesis.
• To differentiate between acquired polycythemia vera and congenital polycythemia using genetic markers.
• To emphasize the role of genetic testing and serum erythropoietin levels in diagnosis.

Main Methods:

• Analysis of JAK2 mutations (exon 14 and exon 12) in peripheral blood for PV.
• Screening for germline mutations in von Hippel-Lindau (VHL) and erythropoietin receptor (EPOR) genes for suspected CP.
• Measurement of serum erythropoietin levels as a complementary diagnostic tool.

Main Results:

• JAK2 mutations (JAK2V617F and exon 12) are highly prevalent in polycythemia vera.
• Germline mutations in VHL or EPOR are associated with congenital polycythemia.
• Serum erythropoietin levels show distinct patterns: decreased in PV, increased in VHL-associated CP, and decreased/normal in EPOR mutation-associated CP.

Conclusions:

• Peripheral blood JAK2 mutation screening is recommended for acquired polycythemia diagnosis.
• VHL and EPOR mutation analysis should be considered for suspected congenital polycythemia.
• Integrated molecular and biochemical testing enhances diagnostic accuracy for polycythemia subtypes.