Polycythemia historical perspective

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Debduti Mukhopadhyay, M.B.B.S[2]

Polycythemia first came into notice by a French physician in the late 1800’s. It was not until 2005 that the main genetic mutation JAK2V617F was implicated in its pathogenesis. William Dameshek was responsible for its inclusion in the group “myeloproliferative disorders”.

• Polycythemia vera was first mentioned in 1892 in the medical literature by a French physician Louis Henri Vaquez.^[1][2][3]

• In 1899 and 1900 two additional cases of polycythemia vera were described by Richard Clark Cabot both with increased erythrocytes and leukocytes and one with marked splenomegaly. ^[4]
• In 1951, William Dameshek grouped together chronic myelogenous leukemia (CML), polycythemia vera, essential thrombocythemia, primary myelofibrosis, and erythroleukemia and coined the term “myeloproliferative disorders”. ^[5]
• In 2005, a gain of function mutation in JAK2 (JAK2V617F) was first implicated in the pathogenesis of BCR–ABL negative myeloproliferative disorders. A liquid culture system was used to culture PV erythroid cells without exogenous cytokines. it was noted that PV erythroid proliferation was inhibited with inhibition of JAK2.

• In 1960, Peter Nowell and David Hungerford published data on an abnormally small chromosome that looked like a Y chromosome, the data came from two male patients with CML. Eventually, seven more cases were discovered, with the presence of a specific chromosomal abnormality.
• Nowell and Hungerford further noticed that these abnormal cells coexisted with normal karyotype, and, thus concluded that the abnormally small chromosome might be a cause of CML rather than coincidental.
• This abnormally small chromosome was named the Philadelphia chromosome, after the city it was discovered in.
• Polycythemia Vera Study Group: Louis Wasserman in 1967 created a group with clinicians from all over the country to study PV in detail. A major significance of this was to study the leukemogenicity of radioactive phosphorus which was one of the major agents used at that time for the treatment of PV.
• Prior to this, the mainstay of treatment was phlebotomy and IV P-32. Other modalities included the following : skeletal radiation therapy, acetyl phenylhydrazine, potassium arsenite, lead acetate, nitrogen mustard, hydroxyurea, melphalan, etc.

The following are a few famous cases of polycythemia vera:

• Phyllis George – A former Miss America and sportscaster, passed away at age 70, due to complications from polycythemia vera on May 14, 2020.