The history of myeloproliferative disorders: Before and after Dameshek

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Abstract

In 1951, William Dameshek described the concept of 'myeloproliferative disorders (MPDs)' by grouping together chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and erythroleukemia; he reasoned that a self-perpetuating trilineage myeloproliferation underlined their pathogenesis. Pre-Dameshek luminaries who laid the foundation for this unifying concept include Bennett, Virchow, Heuck, Vaquez, Osler, Di Guglielmo and Epstein. In 1960, Nowell and Hungerford discovered the Philadelphia (Ph) chromosome in CML. In 1967, Fialkow and colleagues used X-linked polymorphisms to establish CML as a clonal stem cell disease. Also in 1967, the PV Study Group was summoned by Louis Wasserman to study the natural history of PV and conduct large-scale clinical trials. In 1972, Janet Rowley deciphered the Ph chromosome as a reciprocal translocation between chromosomes 9 and 22, thus paving the way for its subsequent characterization as an oncogenic BCR-ABL mutation. In 1996, Brian Druker discovered imatinib - a small molecule ABL inhibitor with exceptional therapeutic activity in CML. In 2005, a gain-of-function JAK2 mutation (JAK2V617F) was described in BCR-ABL-negative MPDs, raising the prospect of a CML-like treatment strategy in PV, ET and PMF. The current review considers these and other landmark events in the history of MPDs.

Original languageEnglish (US)
Pages (from-to)3-13
Number of pages11
JournalLeukemia
Volume22
Issue number1
DOIs
StatePublished - Jan 2008

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Myeloproliferative Disorders
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Polycythemia Vera
History
Essential Thrombocythemia
Philadelphia Chromosome
Primary Myelofibrosis
Chromosomes, Human, Pair 22
Leukemia, Erythroblastic, Acute
Chromosomes, Human, Pair 9
Mutation
Stem Cells
Clinical Trials

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

The history of myeloproliferative disorders : Before and after Dameshek. / Tefferi, Ayalew.

In: Leukemia, Vol. 22, No. 1, 01.2008, p. 3-13.

Research output: Contribution to journalArticle

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