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  1. The classic myeloproliferative neoplasms, including chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are a phenotypically diverse category of malignancies that are derived from stem cells in the myeloid lineage.

  2. The first genetic alteration recognized as a cause of myeloproliferative disease was the translocation that creates the BCR-ABL gene fusion. Recently, activating mutations in JAK2 and MPL have been found in the majority of BCR-ABL-negative myeloproliferative neoplasms. Recurrent mutations in these genes provide clinically useful diagnostic markers.

  3. Implicated by mutational evidence, the JAK-STAT pathway is a rational target for drug development. A number of anti-JAK2 drugs have undergone preclinical testing, and some of these have been introduced into clinical trials.

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