TY - JOUR
T1 - BCR-ABL1-negative myeloproliferative neoplasms
T2 - A review of molecular biology, diagnosis, and treatment
AU - Vakil, Erik
AU - Tefferi, Ayalew
PY - 2011/6
Y1 - 2011/6
N2 - In 2008, the World Health Organization expanded the classification of myeloproliferative disorders based on increasing amounts of molecular and cytogenetic data. Myeloproliferative neoplasms (MPN) that do not contain the BCR-ABL1 mutation include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). JAK2V617F is the best characterized mutation in BCR-ABL1-negative neoplasms, with an estimated prevalence of more than 95% in PV, 50% in ET, and 50% in PMF. Current diagnostic strategies are increasingly reliant on molecular markers, and their prognostic value continues to be investigated. The use of aspirin, hydroxyurea, and phlebotomy for PV and ET, and the use of androgens, steroids, chemotherapy, and radiation therapy for PMF continues to be the mainstay of therapy. The only potentially curative therapy is allogeneic hematopoietic stem cell transplantation, but treatment-related mortality remains high. There have been promising results from clinical trials that involve the JAK tyrosine kinase inhibitors TG101384 and INCB018424, but their role in future therapy is yet to be established. Despite the optimism, it is increasingly apparent that pathogenicity in BCR-ABL1-negative MPN is more complex than for chronic myeloid leukemia, and a pathognomonic mutation may not be forthcoming.
AB - In 2008, the World Health Organization expanded the classification of myeloproliferative disorders based on increasing amounts of molecular and cytogenetic data. Myeloproliferative neoplasms (MPN) that do not contain the BCR-ABL1 mutation include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). JAK2V617F is the best characterized mutation in BCR-ABL1-negative neoplasms, with an estimated prevalence of more than 95% in PV, 50% in ET, and 50% in PMF. Current diagnostic strategies are increasingly reliant on molecular markers, and their prognostic value continues to be investigated. The use of aspirin, hydroxyurea, and phlebotomy for PV and ET, and the use of androgens, steroids, chemotherapy, and radiation therapy for PMF continues to be the mainstay of therapy. The only potentially curative therapy is allogeneic hematopoietic stem cell transplantation, but treatment-related mortality remains high. There have been promising results from clinical trials that involve the JAK tyrosine kinase inhibitors TG101384 and INCB018424, but their role in future therapy is yet to be established. Despite the optimism, it is increasingly apparent that pathogenicity in BCR-ABL1-negative MPN is more complex than for chronic myeloid leukemia, and a pathognomonic mutation may not be forthcoming.
KW - Cytogenetics
KW - Diagnostic strategy
KW - Oncogenes
UR - http://www.scopus.com/inward/record.url?scp=84859022243&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859022243&partnerID=8YFLogxK
U2 - 10.1016/j.clml.2011.04.002
DO - 10.1016/j.clml.2011.04.002
M3 - Article
C2 - 22035746
AN - SCOPUS:84859022243
SN - 2152-2650
VL - 11
SP - S37-S45
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - SUPPL.1
ER -