In vitro expansion of erythroid progenitors from polycythemia vera patients leads to decrease in JAK2 V617F allele

Area of Science:

• Hematology
• Molecular Biology
• Oncology

Background:

• The JAK2(V617F) mutation is found in over 80% of polycythemia vera (PV) patients.
• This mutation is thought to cause erythropoietin-independent proliferation of erythroid progenitor cells.
• However, its exact role is questioned as it's not dominant, not PV-specific, and absent in some PV patients.

Purpose of the Study:

• To investigate the relative frequency of the JAK2(V617F) mutation in in vitro-expanded PV progenitors.
• To clarify the role of JAK2(V617F) in the pathogenesis and clonal evolution of PV.

Main Methods:

• Optimized in vitro expansion of erythroid progenitors from mononuclear cells.
• Measured JAK2(V617F) allele frequency using allele-specific real-time polymerase chain reaction.
• Assessed clonality using established procedures.

Main Results:

• JAK2(V617F) allele frequency decreased in expanded PV erythroid progenitors and dendritic cells compared to granulocytes.
• Expanded erythroid cells were polyclonal, while granulocytes were clonal.
• Expanded PV erythroid progenitors showed a twofold increased proliferative capacity versus healthy controls.
• Erythropoietin favored cells lacking the JAK2(V617F) allele.

Conclusions:

• The JAK2(V617F) mutation does not provide a proliferative or survival advantage to PV clones during in vitro expansion.
• These findings suggest JAK2(V617F) is important in PV biology but may not be the initiating event.