Polycythemia Vera: An Appraisal of the Biology and Management 10 Years After the Discovery of JAK2 V617F.
Polycythemia vera (PV) is a chronic myeloproliferative neoplasm that is associated with a substantial symptom burden, thrombohemorrhagic complications, and impaired survival. A decade after the seminal discovery of an activating mutation in the tyrosine kinase JAK2 in nearly all patients with PV, new treatment options are finally beginning to emerge, necessitating a critical reappraisal of the underlying pathogenesis and therapeutic modalities available for PV. Herein, we comprehensively review clinical aspects of PV including diagnostic considerations, natural history, and risk factors for thrombosis. We summarize recent studies delineating the genetic basis of PV, including their implications for evolution to myelofibrosis and secondary acute myeloid leukemia. We assess the quality of evidence to support the use of currently available therapies, including aspirin, phlebotomy, hydroxyurea, and interferon. We analyze recent studies evaluating the safety and efficacy of JAK inhibitors, such as ruxolitinib, and evaluate their role in the context of other available therapies for PV. This review provides a framework for practicing hematologists and oncologists to make rational treatment decisions for patients with PV.
Brady L. Stein, Northwestern Feinberg University School of Medicine, Chicago, IL; Stephen T. Oh and Camille Abboud, Washington University School of Medicine, St Louis, MO; Dmitriy Berenzon, Wake Forest University School of Medicine, Winston Salem, NC; Gabriela S. Hobbs, Massachusetts General Hospital, Boston, MA; Marina Kremyanskaya, John Mascarenhas, and Ronald Hoffman, Mount Sinai School of Medicine; Raajit K. Rampal, Memorial Sloan Kettering Cancer Center; Mark L. Heaney, Columbia University Medical Center; Ellen K. Ritchie, Cornell University School of Medicine, New York, NY; Kenneth Adler, Regional Cancer Care Associates, Morristown, NJ; Elias J. Jabbour, MD Anderson Cancer Center; Lawrence Rice, Cornell Houston Methodist Hospital, Houston, TX; Rami S. Komrokji, Moffitt Cancer Center, Tampa, FL; and Alison R. Moliterno, Johns Hopkins University School of Medicine, Baltimore, MD.
Brady L
BL
Stein
Brady L. Stein, Northwestern Feinberg University School of Medicine, Chicago, IL; Stephen T. Oh and Camille Abboud, Washington University School of Medicine, St Louis, MO; Dmitriy Berenzon, Wake Forest University School of Medicine, Winston Salem, NC; Gabriela S. Hobbs, Massachusetts General Hospital, Boston, MA; Marina Kremyanskaya, John Mascarenhas, and Ronald Hoffman, Mount Sinai School of Medicine; Raajit K. Rampal, Memorial Sloan Kettering Cancer Center; Mark L. Heaney, Columbia University Medical Center; Ellen K. Ritchie, Cornell University School of Medicine, New York, NY; Kenneth Adler, Regional Cancer Care Associates, Morristown, NJ; Elias J. Jabbour, MD Anderson Cancer Center; Lawrence Rice, Cornell Houston Methodist Hospital, Houston, TX; Rami S. Komrokji, Moffitt Cancer Center, Tampa, FL; and Alison R. Moliterno, Johns Hopkins University School of Medicine, Baltimore, MD.
Stephen T
ST
Oh
Brady L. Stein, Northwestern Feinberg University School of Medicine, Chicago, IL; Stephen T. Oh and Camille Abboud, Washington University School of Medicine, St Louis, MO; Dmitriy Berenzon, Wake Forest University School of Medicine, Winston Salem, NC; Gabriela S. Hobbs, Massachusetts General Hospital, Boston, MA; Marina Kremyanskaya, John Mascarenhas, and Ronald Hoffman, Mount Sinai School of Medicine; Raajit K. Rampal, Memorial Sloan Kettering Cancer Center; Mark L. Heaney, Columbia University Medical Center; Ellen K. Ritchie, Cornell University School of Medicine, New York, NY; Kenneth Adler, Regional Cancer Care Associates, Morristown, NJ; Elias J. Jabbour, MD Anderson Cancer Center; Lawrence Rice, Cornell Houston Methodist Hospital, Houston, TX; Rami S. Komrokji, Moffitt Cancer Center, Tampa, FL; and Alison R. Moliterno, Johns Hopkins University School of Medicine, Baltimore, MD.
Dmitriy
D
Berenzon
Brady L. Stein, Northwestern Feinberg University School of Medicine, Chicago, IL; Stephen T. Oh and Camille Abboud, Washington University School of Medicine, St Louis, MO; Dmitriy Berenzon, Wake Forest University School of Medicine, Winston Salem, NC; Gabriela S. Hobbs, Massachusetts General Hospital, Boston, MA; Marina Kremyanskaya, John Mascarenhas, and Ronald Hoffman, Mount Sinai School of Medicine; Raajit K. Rampal, Memorial Sloan Kettering Cancer Center; Mark L. Heaney, Columbia University Medical Center; Ellen K. Ritchie, Cornell University School of Medicine, New York, NY; Kenneth Adler, Regional Cancer Care Associates, Morristown, NJ; Elias J. Jabbour, MD Anderson Cancer Center; Lawrence Rice, Cornell Houston Methodist Hospital, Houston, TX; Rami S. Komrokji, Moffitt Cancer Center, Tampa, FL; and Alison R. Moliterno, Johns Hopkins University School of Medicine, Baltimore, MD.
Gabriela S
GS
Hobbs
Brady L. Stein, Northwestern Feinberg University School of Medicine, Chicago, IL; Stephen T. Oh and Camille Abboud, Washington University School of Medicine, St Louis, MO; Dmitriy Berenzon, Wake Forest University School of Medicine, Winston Salem, NC; Gabriela S. Hobbs, Massachusetts General Hospital, Boston, MA; Marina Kremyanskaya, John Mascarenhas, and Ronald Hoffman, Mount Sinai School of Medicine; Raajit K. Rampal, Memorial Sloan Kettering Cancer Center; Mark L. Heaney, Columbia University Medical Center; Ellen K. Ritchie, Cornell University School of Medicine, New York, NY; Kenneth Adler, Regional Cancer Care Associates, Morristown, NJ; Elias J. Jabbour, MD Anderson Cancer Center; Lawrence Rice, Cornell Houston Methodist Hospital, Houston, TX; Rami S. Komrokji, Moffitt Cancer Center, Tampa, FL; and Alison R. Moliterno, Johns Hopkins University School of Medicine, Baltimore, MD.
Marina
M
Kremyanskaya
Brady L. Stein, Northwestern Feinberg University School of Medicine, Chicago, IL; Stephen T. Oh and Camille Abboud, Washington University School of Medicine, St Louis, MO; Dmitriy Berenzon, Wake Forest University School of Medicine, Winston Salem, NC; Gabriela S. Hobbs, Massachusetts General Hospital, Boston, MA; Marina Kremyanskaya, John Mascarenhas, and Ronald Hoffman, Mount Sinai School of Medicine; Raajit K. Rampal, Memorial Sloan Kettering Cancer Center; Mark L. Heaney, Columbia University Medical Center; Ellen K. Ritchie, Cornell University School of Medicine, New York, NY; Kenneth Adler, Regional Cancer Care Associates, Morristown, NJ; Elias J. Jabbour, MD Anderson Cancer Center; Lawrence Rice, Cornell Houston Methodist Hospital, Houston, TX; Rami S. Komrokji, Moffitt Cancer Center, Tampa, FL; and Alison R. Moliterno, Johns Hopkins University School of Medicine, Baltimore, MD.
Raajit K
RK
Rampal
Brady L. Stein, Northwestern Feinberg University School of Medicine, Chicago, IL; Stephen T. Oh and Camille Abboud, Washington University School of Medicine, St Louis, MO; Dmitriy Berenzon, Wake Forest University School of Medicine, Winston Salem, NC; Gabriela S. Hobbs, Massachusetts General Hospital, Boston, MA; Marina Kremyanskaya, John Mascarenhas, and Ronald Hoffman, Mount Sinai School of Medicine; Raajit K. Rampal, Memorial Sloan Kettering Cancer Center; Mark L. Heaney, Columbia University Medical Center; Ellen K. Ritchie, Cornell University School of Medicine, New York, NY; Kenneth Adler, Regional Cancer Care Associates, Morristown, NJ; Elias J. Jabbour, MD Anderson Cancer Center; Lawrence Rice, Cornell Houston Methodist Hospital, Houston, TX; Rami S. Komrokji, Moffitt Cancer Center, Tampa, FL; and Alison R. Moliterno, Johns Hopkins University School of Medicine, Baltimore, MD.
Camille N
CN
Abboud
Brady L. Stein, Northwestern Feinberg University School of Medicine, Chicago, IL; Stephen T. Oh and Camille Abboud, Washington University School of Medicine, St Louis, MO; Dmitriy Berenzon, Wake Forest University School of Medicine, Winston Salem, NC; Gabriela S. Hobbs, Massachusetts General Hospital, Boston, MA; Marina Kremyanskaya, John Mascarenhas, and Ronald Hoffman, Mount Sinai School of Medicine; Raajit K. Rampal, Memorial Sloan Kettering Cancer Center; Mark L. Heaney, Columbia University Medical Center; Ellen K. Ritchie, Cornell University School of Medicine, New York, NY; Kenneth Adler, Regional Cancer Care Associates, Morristown, NJ; Elias J. Jabbour, MD Anderson Cancer Center; Lawrence Rice, Cornell Houston Methodist Hospital, Houston, TX; Rami S. Komrokji, Moffitt Cancer Center, Tampa, FL; and Alison R. Moliterno, Johns Hopkins University School of Medicine, Baltimore, MD.
Kenneth
K
Adler
Brady L. Stein, Northwestern Feinberg University School of Medicine, Chicago, IL; Stephen T. Oh and Camille Abboud, Washington University School of Medicine, St Louis, MO; Dmitriy Berenzon, Wake Forest University School of Medicine, Winston Salem, NC; Gabriela S. Hobbs, Massachusetts General Hospital, Boston, MA; Marina Kremyanskaya, John Mascarenhas, and Ronald Hoffman, Mount Sinai School of Medicine; Raajit K. Rampal, Memorial Sloan Kettering Cancer Center; Mark L. Heaney, Columbia University Medical Center; Ellen K. Ritchie, Cornell University School of Medicine, New York, NY; Kenneth Adler, Regional Cancer Care Associates, Morristown, NJ; Elias J. Jabbour, MD Anderson Cancer Center; Lawrence Rice, Cornell Houston Methodist Hospital, Houston, TX; Rami S. Komrokji, Moffitt Cancer Center, Tampa, FL; and Alison R. Moliterno, Johns Hopkins University School of Medicine, Baltimore, MD.
Mark L
ML
Heaney
Brady L. Stein, Northwestern Feinberg University School of Medicine, Chicago, IL; Stephen T. Oh and Camille Abboud, Washington University School of Medicine, St Louis, MO; Dmitriy Berenzon, Wake Forest University School of Medicine, Winston Salem, NC; Gabriela S. Hobbs, Massachusetts General Hospital, Boston, MA; Marina Kremyanskaya, John Mascarenhas, and Ronald Hoffman, Mount Sinai School of Medicine; Raajit K. Rampal, Memorial Sloan Kettering Cancer Center; Mark L. Heaney, Columbia University Medical Center; Ellen K. Ritchie, Cornell University School of Medicine, New York, NY; Kenneth Adler, Regional Cancer Care Associates, Morristown, NJ; Elias J. Jabbour, MD Anderson Cancer Center; Lawrence Rice, Cornell Houston Methodist Hospital, Houston, TX; Rami S. Komrokji, Moffitt Cancer Center, Tampa, FL; and Alison R. Moliterno, Johns Hopkins University School of Medicine, Baltimore, MD.
Elias J
EJ
Jabbour
Brady L. Stein, Northwestern Feinberg University School of Medicine, Chicago, IL; Stephen T. Oh and Camille Abboud, Washington University School of Medicine, St Louis, MO; Dmitriy Berenzon, Wake Forest University School of Medicine, Winston Salem, NC; Gabriela S. Hobbs, Massachusetts General Hospital, Boston, MA; Marina Kremyanskaya, John Mascarenhas, and Ronald Hoffman, Mount Sinai School of Medicine; Raajit K. Rampal, Memorial Sloan Kettering Cancer Center; Mark L. Heaney, Columbia University Medical Center; Ellen K. Ritchie, Cornell University School of Medicine, New York, NY; Kenneth Adler, Regional Cancer Care Associates, Morristown, NJ; Elias J. Jabbour, MD Anderson Cancer Center; Lawrence Rice, Cornell Houston Methodist Hospital, Houston, TX; Rami S. Komrokji, Moffitt Cancer Center, Tampa, FL; and Alison R. Moliterno, Johns Hopkins University School of Medicine, Baltimore, MD.
Rami S
RS
Komrokji
Brady L. Stein, Northwestern Feinberg University School of Medicine, Chicago, IL; Stephen T. Oh and Camille Abboud, Washington University School of Medicine, St Louis, MO; Dmitriy Berenzon, Wake Forest University School of Medicine, Winston Salem, NC; Gabriela S. Hobbs, Massachusetts General Hospital, Boston, MA; Marina Kremyanskaya, John Mascarenhas, and Ronald Hoffman, Mount Sinai School of Medicine; Raajit K. Rampal, Memorial Sloan Kettering Cancer Center; Mark L. Heaney, Columbia University Medical Center; Ellen K. Ritchie, Cornell University School of Medicine, New York, NY; Kenneth Adler, Regional Cancer Care Associates, Morristown, NJ; Elias J. Jabbour, MD Anderson Cancer Center; Lawrence Rice, Cornell Houston Methodist Hospital, Houston, TX; Rami S. Komrokji, Moffitt Cancer Center, Tampa, FL; and Alison R. Moliterno, Johns Hopkins University School of Medicine, Baltimore, MD.
Alison R
AR
Moliterno
Brady L. Stein, Northwestern Feinberg University School of Medicine, Chicago, IL; Stephen T. Oh and Camille Abboud, Washington University School of Medicine, St Louis, MO; Dmitriy Berenzon, Wake Forest University School of Medicine, Winston Salem, NC; Gabriela S. Hobbs, Massachusetts General Hospital, Boston, MA; Marina Kremyanskaya, John Mascarenhas, and Ronald Hoffman, Mount Sinai School of Medicine; Raajit K. Rampal, Memorial Sloan Kettering Cancer Center; Mark L. Heaney, Columbia University Medical Center; Ellen K. Ritchie, Cornell University School of Medicine, New York, NY; Kenneth Adler, Regional Cancer Care Associates, Morristown, NJ; Elias J. Jabbour, MD Anderson Cancer Center; Lawrence Rice, Cornell Houston Methodist Hospital, Houston, TX; Rami S. Komrokji, Moffitt Cancer Center, Tampa, FL; and Alison R. Moliterno, Johns Hopkins University School of Medicine, Baltimore, MD.
Ellen K
EK
Ritchie
Brady L. Stein, Northwestern Feinberg University School of Medicine, Chicago, IL; Stephen T. Oh and Camille Abboud, Washington University School of Medicine, St Louis, MO; Dmitriy Berenzon, Wake Forest University School of Medicine, Winston Salem, NC; Gabriela S. Hobbs, Massachusetts General Hospital, Boston, MA; Marina Kremyanskaya, John Mascarenhas, and Ronald Hoffman, Mount Sinai School of Medicine; Raajit K. Rampal, Memorial Sloan Kettering Cancer Center; Mark L. Heaney, Columbia University Medical Center; Ellen K. Ritchie, Cornell University School of Medicine, New York, NY; Kenneth Adler, Regional Cancer Care Associates, Morristown, NJ; Elias J. Jabbour, MD Anderson Cancer Center; Lawrence Rice, Cornell Houston Methodist Hospital, Houston, TX; Rami S. Komrokji, Moffitt Cancer Center, Tampa, FL; and Alison R. Moliterno, Johns Hopkins University School of Medicine, Baltimore, MD.
Lawrence
L
Rice
Brady L. Stein, Northwestern Feinberg University School of Medicine, Chicago, IL; Stephen T. Oh and Camille Abboud, Washington University School of Medicine, St Louis, MO; Dmitriy Berenzon, Wake Forest University School of Medicine, Winston Salem, NC; Gabriela S. Hobbs, Massachusetts General Hospital, Boston, MA; Marina Kremyanskaya, John Mascarenhas, and Ronald Hoffman, Mount Sinai School of Medicine; Raajit K. Rampal, Memorial Sloan Kettering Cancer Center; Mark L. Heaney, Columbia University Medical Center; Ellen K. Ritchie, Cornell University School of Medicine, New York, NY; Kenneth Adler, Regional Cancer Care Associates, Morristown, NJ; Elias J. Jabbour, MD Anderson Cancer Center; Lawrence Rice, Cornell Houston Methodist Hospital, Houston, TX; Rami S. Komrokji, Moffitt Cancer Center, Tampa, FL; and Alison R. Moliterno, Johns Hopkins University School of Medicine, Baltimore, MD.
John
J
Mascarenhas
Brady L. Stein, Northwestern Feinberg University School of Medicine, Chicago, IL; Stephen T. Oh and Camille Abboud, Washington University School of Medicine, St Louis, MO; Dmitriy Berenzon, Wake Forest University School of Medicine, Winston Salem, NC; Gabriela S. Hobbs, Massachusetts General Hospital, Boston, MA; Marina Kremyanskaya, John Mascarenhas, and Ronald Hoffman, Mount Sinai School of Medicine; Raajit K. Rampal, Memorial Sloan Kettering Cancer Center; Mark L. Heaney, Columbia University Medical Center; Ellen K. Ritchie, Cornell University School of Medicine, New York, NY; Kenneth Adler, Regional Cancer Care Associates, Morristown, NJ; Elias J. Jabbour, MD Anderson Cancer Center; Lawrence Rice, Cornell Houston Methodist Hospital, Houston, TX; Rami S. Komrokji, Moffitt Cancer Center, Tampa, FL; and Alison R. Moliterno, Johns Hopkins University School of Medicine, Baltimore, MD. ronald.hoffman@mssm.edu.
Ronald
R
Hoffman
D001241:Aspirin / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D018450:Disease Progression; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D015994:Incidence; D016899:Interferon-beta / Q000627:therapeutic use*; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D018962:Phlebotomy / Q000379:methods; D017354:Point Mutation; D011087:Polycythemia Vera / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D016896:Treatment Outcome
D011092:Polyethylene Glycols; D016899:Interferon-beta; D053614:Janus Kinase 2; C428112:peginterferon beta-1a; D001241:Aspirin; D006918:Hydroxyurea