Myeloproliferative Neoplasms: The Role of Molecular Markers

1. LeiLani Collins, MS, MT(ASCP)SH[⇑][1] 1. University of Tennessee Health Science Center, Memphis, TN 1. Address for Correspondence: LeiLani Collins, MS, MT(ASCP)SH , University of Tennessee Health Science Center, 930 Madison Ave., Ste. 670, Memphis, TN 38163, 901-448-6299, Fax: 901-448-7545, lcollins{at}uthsc.edu After reading this article, the reader will be able to: 1. Describe the fusion gene formed as a result of the translocation t(9;22)(q34;q11) in chronic myelogenous leukemia. 2. Describe common symptoms of Philadelphia chromosome negative myeloproliferative neoplasms. 3. State the frequency of the occurrence of the JAK2 V617F mutation in PV, ET, and PMF. 4. Describe the significance of the JAK2 mutation in the diagnosis of PV, ET, and PMF. 5. Describe the significance of tyrosine kinase inhibitors on the treatment of MPNs. 6. Define current treatment for Philadelphia chromosome negative MPNs. 7. Describe the significance of imatinib treatment for CML on treatment for the other MPNs. The myeloproliferative neoplasms (MPN), formerly known as the myeloproliferative disorders (MPD), are a group of clonal disorders involving hyperproliferation of one or more of the myeloid cell lines (erythrocytic, granulocytic, megakaryocytic). The most common disorders traditionally classified as MPNs are chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Other, less common disorders in this group include chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia (CEL), mastocytosis, and myeloproliferative neoplasm, unclassifiable (MPN,U).1 All of these neoplasms are most common in people with a median age of 65 years at diagnosis but have been diagnosed in all age groups. Common presenting signs are fatigue, splenomegaly, and elevated cell counts. Often, there are bleeding or thrombotic symptoms. Chronic Myelogenous Leukemia (CML)— BCR/ABL1 -Positive MPN CML is a disease of “firsts” that has led the way for diagnostic, treatment, and prognostic factors for the other MPNs. It is the first disorder for which the term “leukemia” was used; the first malignancy associated with a recurring chromosomal abnormality (Philadelphia chromosome); the first disease in which the chromosomal abnormality formed a fusion gene ( BCR/ABL1 ); the first disease in which a protein fundamental to the pathogenesis of the disease was identified; and, the first disorder in which a therapeutic agent specifically targeted the molecular defect to effectively treat the disorder.1 Historically, CML was the first MPN to have a known acquired chromosomal abnormality, a reciprocal translocation between the long arms of chromosomes 9 and 22 known as the Philadelphia chromosome (Ph1) and designated as… After reading this article, the reader will be able to: 1. Describe the fusion gene formed as a result of the translocation t(9;22)(q34;q11) in chronic myelogenous leukemia. 2. Describe common symptoms of Philadelphia chromosome negative myeloproliferative neoplasms. 3. State the frequency of the occurrence of the JAK2 V617F mutation in PV, ET, and PMF. 4. Describe the significance of the JAK2 mutation in the diagnosis of PV, ET, and PMF. 5. Describe the significance of tyrosine kinase inhibitors on the treatment of MPNs. 6. Define current treatment for Philadelphia chromosome negative MPNs. 7. Describe the significance of imatinib treatment for CML on treatment for the other MPNs. [1]: #corresp-1