Data-driven analysis of JAK2V617F kinetics during interferon-alpha2 treatment of patients with polycythemia vera and related neoplasms.
Adult
Aged
Alleles
Female
Humans
Interferon alpha-2
/ administration & dosage
Interferon-alpha
/ administration & dosage
Janus Kinase 2
/ blood
Male
Middle Aged
Polycythemia Vera
/ blood
Polyethylene Glycols
/ administration & dosage
Polymorphism, Single Nucleotide
Primary Myelofibrosis
/ blood
Prospective Studies
Real-Time Polymerase Chain Reaction
Recombinant Proteins
/ administration & dosage
Retrospective Studies
Thrombocythemia, Essential
/ blood
Time Factors
Time-to-Treatment
Treatment Outcome
JAK2V617F kinetics
early treatment
essential thrombocythemia
interferon-alpha2
myeloproliferative neoplasms
polycythemia vera
primary myelofibrosis
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
12
04
2019
revised:
13
11
2019
accepted:
15
11
2019
pubmed:
29
1
2020
medline:
24
4
2021
entrez:
29
1
2020
Statut:
ppublish
Résumé
Treatment with PEGylated interferon-alpha2 (IFN) of patients with essential thrombocythemia and polycythemia vera induces major molecular remissions with a reduction in the JAK2V617F allele burden to undetectable levels in a subset of patients. A favorable response to IFN has been argued to depend upon the tumor burden, implying that institution of treatment with IFN should be as early as possible after the diagnosis. However, evidence for this statement is not available. We present a thorough analysis of unique serial JAK2V617F measurements in 66 IFN-treated patients and in 6 untreated patients. Without IFN treatment, the JAK2V617F allele burden increased exponentially with a period of doubling of 1.4 year. During monotherapy with IFN, the JAK2V617F allele burden decreased mono- or bi-exponentially for 33 responders of which 28 patients satisfied both descriptions. Bi-exponential description improved the fits in 19 cases being associated with late JAK2V617F responses. The decay of the JAK2V617F allele burden during IFN treatment was estimated to have half-lives of 1.6 year for the monoexponential response and 1.0 year in the long term for the bi-exponential response. In conclusion, through data-driven analysis of the JAK2V617F allele burden, we provide novel information regarding the JAK2V617F kinetics during IFN-treatment, arguing for early intervention.
Identifiants
pubmed: 31991066
doi: 10.1002/cam4.2741
pmc: PMC7064092
doi:
Substances chimiques
Interferon alpha-2
0
Interferon-alpha
0
Recombinant Proteins
0
Polyethylene Glycols
3WJQ0SDW1A
JAK2 protein, human
EC 2.7.10.2
Janus Kinase 2
EC 2.7.10.2
peginterferon alfa-2b
G8RGG88B68
peginterferon alfa-2a
Q46947FE7K
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2039-2051Informations de copyright
© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Références
Nature. 2005 Apr 28;434(7037):1144-8
pubmed: 15793561
Exp Hematol Oncol. 2017 Nov 9;6:30
pubmed: 29152412
J Clin Oncol. 2011 Jun 10;29(17):2410-5
pubmed: 21537037
Mediators Inflamm. 2015;2015:606819
pubmed: 26538830
Blood. 2009 May 14;113(20):4829-33
pubmed: 19278953
Blood. 2015 Dec 10;126(24):2585-91
pubmed: 26486786
Nature. 2018 Sep;561(7724):473-478
pubmed: 30185910
Blood. 2011 May 12;117(19):5019-32
pubmed: 21300984
Ann Hematol. 2008 Oct;87(10):847-50
pubmed: 18481066
Br J Haematol. 2005 Oct;131(2):208-13
pubmed: 16197451
Blood. 2007 Mar 15;109(6):2310-3
pubmed: 17110452
Lancet. 2005 Mar 19-25;365(9464):1054-61
pubmed: 15781101
Blood. 2013 Aug 8;122(6):893-901
pubmed: 23782935
Leuk Res. 2013 Feb;37(2):214-20
pubmed: 23174192
Leukemia. 2018 Aug;32(8):1830-1833
pubmed: 29556018
Lancet Haematol. 2017 Apr;4(4):e165-e175
pubmed: 28291640
Leukemia. 2007 Sep;21(9):2074-5
pubmed: 17476276
Eur J Intern Med. 2015 Jun;26(5):344-7
pubmed: 25863408
Blood. 2012 Apr 5;119(14):3219-25
pubmed: 22318201
Semin Thromb Hemost. 2006 Jun;32(4 Pt 2):381-98
pubmed: 16810614
N Engl J Med. 2006 Dec 7;355(23):2452-66
pubmed: 17151367
Leukemia. 2016 Apr;30(4):776-81
pubmed: 26601783
Br J Haematol. 2006 Jan;132(2):244-5
pubmed: 16398659
Exp Hematol. 2007 May;35(5):702-11
pubmed: 17577920
Blood. 2015 Oct 8;126(15):1762-9
pubmed: 26261238
Nature. 2018 Jan 24;553(7689):418-426
pubmed: 29364285
Cancer Cell. 2005 Apr;7(4):387-97
pubmed: 15837627
Leuk Lymphoma. 2016 Feb;57(2):348-354
pubmed: 25956046
J Hematol Oncol. 2017 Jan 13;10(1):15
pubmed: 28086927
Blood. 2008 Oct 15;112(8):3065-72
pubmed: 18650451
Exp Hematol. 2007 Nov;35(11):1704-7
pubmed: 17920754
Blood. 2006 May 1;107(9):3676-82
pubmed: 16373657
Blood. 2014 Jun 12;123(24):3714-9
pubmed: 24786775
Cancer Med. 2020 Mar;9(6):2039-2051
pubmed: 31991066
Cancer. 2006 Aug 1;107(3):451-8
pubmed: 16804923
Curr Drug Targets. 2011 Mar 1;12(3):392-419
pubmed: 21143149
Expert Rev Hematol. 2011 Dec;4(6):637-55
pubmed: 22077528
Am J Hematol. 2015 Apr;90(4):288-94
pubmed: 25545244
Leuk Res. 2017 Mar;54:73-77
pubmed: 28113109
N Engl J Med. 2013 Dec 19;369(25):2391-2405
pubmed: 24325359
Mediators Inflamm. 2015;2015:453020
pubmed: 26491227
Expert Rev Hematol. 2013 Feb;6(1):49-58
pubmed: 23373780
J Clin Oncol. 2005 Apr 1;23(10):2224-32
pubmed: 15710945
Blood. 2007 Aug 1;110(3):840-6
pubmed: 17379742
Semin Immunopathol. 2019 Jan;41(1):5-19
pubmed: 30203226
Cancer. 2007 Jun 1;109(11):2279-84
pubmed: 17440984
Eur J Haematol. 2007 Dec;79(6):508-15
pubmed: 17961178
Leukemia. 2013 Oct;27(10):2032-9
pubmed: 23860450
Cytokine Growth Factor Rev. 2013 Apr;24(2):133-45
pubmed: 23415024
Curr Hematol Malig Rep. 2017 Oct;12(5):406-414
pubmed: 28948521
Leuk Res. 2013 Sep;37(9):1041-5
pubmed: 23827351
PLoS One. 2012;7(4):e35631
pubmed: 22536419
Expert Rev Hematol. 2017 May;10(5):393-404
pubmed: 28402197
Haematologica. 2006 Feb;91(2):169-75
pubmed: 16461300
J Interferon Cytokine Res. 2013 Apr;33(4):145-53
pubmed: 23570380
Mediators Inflamm. 2015;2015:102476
pubmed: 26604428
Blood. 2002 Oct 1;100(7):2665-7
pubmed: 12239184
N Engl J Med. 2013 Dec 19;369(25):2379-90
pubmed: 24325356
Haematologica. 2008 Dec;93(12):1890-3
pubmed: 18790796
Blood. 2014 Apr 3;123(14):2220-8
pubmed: 24478400
PLoS One. 2016 Oct 20;11(10):e0165336
pubmed: 27764253
Cancer. 2006 Jun 1;106(11):2397-405
pubmed: 16639737
J Clin Oncol. 2009 Nov 10;27(32):5418-24
pubmed: 19826111
Blood. 2006 Sep 15;108(6):2037-40
pubmed: 16709929
Hematology. 2009 Dec;14(6):331-4
pubmed: 19941739
Leukemia. 2007 Sep;21(9):1952-9
pubmed: 17625606
Expert Rev Hematol. 2015 Aug;8(4):439-45
pubmed: 25996953
Cancer. 2006 Feb 1;106(3):631-5
pubmed: 16369984
N Engl J Med. 2005 Apr 28;352(17):1779-90
pubmed: 15858187
Br J Haematol. 2007 Mar;136(5):745-51
pubmed: 17313377