An accurate, simple prognostic model consisting of age, JAK2, CALR, and MPL mutation status for patients with primary myelofibrosis.
In most patients with primary myelofibrosis, one of three mutually exclusive somatic mutations is detected. In approximately 60% of patients, the Janus kinase 2 gene is mutated, in 20%, the calreticulin gene is mutated, and in 5%, the myeloproliferative leukemia virus gene is mutated. Although patients with mutated calreticulin or myeloproliferative leukemia genes have a favorable outcome, and those with none of these mutations have an unfavorable outcome, prognostication based on mutation status is challenging due to the heterogeneous survival of patients with mutated Janus kinase 2. To develop a prognostic model based on mutation status, we screened primary myelofibrosis patients seen at the MD Anderson Cancer Center, Houston, USA, between 2000 and 2013 for the presence of Janus kinase 2, calreticulin, and myeloproliferative leukemia mutations. Of 344 primary myelofibrosis patients, Janus kinase 2V617Fwas detected in 226 (66%), calreticulin mutation in 43 (12%), and myeloproliferative leukemia mutation in 16 (5%); 59 patients (17%) were triple-negatives. A 50% cut-off dichotomized Janus kinase 2-mutated patients into those with high Janus kinase 2V617Fallele burden and favorable survival and those with low Janus kinase 2V617Fallele burden and unfavorable survival. Patients with a favorable mutation status (high Janus kinase 2V617Fallele burden/myeloproliferative leukemia/calreticulin mutation) and aged 65 years or under had a median survival of 126 months. Patients with one risk factor (low Janus kinase 2V617Fallele burden/triple-negative or age >65 years) had an intermediate survival duration, and patients aged over 65 years with an adverse mutation status (low Janus kinase 2V617Fallele burden or triple-negative) had a median survival of only 35 months. Our simple and easily applied age- and mutation status-based scoring system accurately predicted the survival of patients with primary myelofibrosis.
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Davidoff Medical Center, Beilinson Hospital, Petah Tikva, Israel.|Tel Aviv University, Sackler School of Medicine, Israel.
Uri
U
Rozovski
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Srdan
S
Verstovsek
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Taghi
T
Manshouri
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|University of Zagreb School of Medicine, Croatian Institute for Brain Research, Croatia.
Vilma
V
Dembitz
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ksenija
K
Bozinovic
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Kate
K
Newberry
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ying
Y
Zhang
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Joseph E
JE
Bove
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sherry
S
Pierce
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Hagop
H
Kantarjian
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA zestrov@mdanderson.org.
Zeev
Z
Estrov
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D037282:Calreticulin / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D011379:Prognosis; D016016:Proportional Hazards Models; D053628:Receptors, Thrombopoietin / Q000235:genetics*
D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D053614:Janus Kinase 2
Blood. 2005 Sep 15;106(6):2162-8
15920007
Blood. 2007 Dec 1;110(12):4030-6
17712047
N Engl J Med. 2013 Dec 19;369(25):2379-90
24325356
Blood. 2014 Aug 14;124(7):1062-9
24986690
Blood. 1996 Aug 1;88(3):1013-8
8704209
Haematologica. 2009 Jan;94(1):38-45
19001280
Leukemia. 2009 May;23(5):905-11
19262601
Blood. 2010 Mar 4;115(9):1703-8
20008785
N Engl J Med. 2013 Dec 19;369(25):2391-405
24325359
Blood. 2009 Mar 26;113(13):2895-901
18988864
Blood. 2006 Nov 15;108(10):3472-6
16868251
Blood Rev. 2016 Nov;30(6):453-459
27341755
Leukemia. 2013 Sep;27(9):1861-9
23619563
Blood. 2009 Jul 30;114(5):937-51
19357394
Clin Cancer Res. 2004 Nov 1;10(21):7252-9
15534099
Blood. 2014 Mar 6;123(10):1544-51
24366362
Leukemia. 2014 Jul;28(7):1568-70
24569778
Exp Hematol. 2007 Jan;35(1):32-8
17198871
N Engl J Med. 2005 Apr 28;352(17):1779-90
15858187
J Clin Oncol. 2009 Nov 20;27(33):5587-93
19786661
Lancet. 2005 Mar 19-25;365(9464):1054-61
15781101
Leukemia. 2008 Apr;22(4):756-61
18216871
Leukemia. 2014 May;28(5):1052-9
24150215
Leuk Res. 2007 Nov;31(11):1503-9
17397921
Blood Cancer J. 2015 Oct 16;5:e360
26473532
J Clin Oncol. 2011 Feb 1;29(4):392-7
21149668
Blood. 2009 Aug 20;114(8):1477-83
19549988
J Clin Oncol. 1999 Sep;17(9):2954-70
10561375
Leukemia. 2014 Jul;28(7):1472-7
24402162
Leukemia. 2010 Jul;24(7):1302-9
20508616
Leuk Lymphoma. 2012 Nov;53(11):2210-3
22524513