Establishing optimal quantitative-polymerase chain reaction assays for routine diagnosis and tracking of minimal residual disease in JAK2-V617F-associated myeloproliferative neoplasms: a joint European LeukemiaNet/MPN&MPNr-EuroNet (COST action BM0902) study

被引：100

作者：

Jovanovic, J. V. ^{[1
]}

Ivey, A. ^{[1
,2
]}

Vannucchi, A. M. ^{[3
]}

Lippert, E. ^{[4
]}

Leibundgut, E. Oppliger ^{[5
,6
]}

Cassinat, B. ^{[7
]}

Pallisgaard, N. ^{[8
]}

Maroc, N. ^{[9
]}

Hermouet, S. ^{[10
]}

Nickless, G. ^{[2
]}

Guglielmelli, P.

van der Reijden, B. A. ^{[11
]}

Jansen, J. H. ^{[11
]}

Alpermann, T. ^{[12
]}

Schnittger, S. ^{[12
]}

Bench, A. ^{[13
,14
]}

Tobal, K. ^{[2
]}

Wilkins, B. ^{[15
]}

Cuthill, K. ^{[16
]}

McLornan, D. ^{[16
]}

Yeoman, K. ^{[1
]}

Akiki, S. ^{[17
]}

Bryon, J. ^{[17
]}

Jeffries, S. ^{[17
]}

Jones, A. ^{[18
]}

Percy, M. J. ^{[19
]}

Schwemmers, S. ^{[20
]}

Gruender, A. ^{[20
]}

Kelley, T. W. ^{[21
]}

Reading, S. ^{[22
]}

Pancrazzi, A. ^{[3
]}

McMullin, M. F. ^{[23
]}

Pahl, H. L. ^{[20
]}

Cross, N. C. P. ^{[18
]}

Harrison, C. N. ^{[24
]}

Prchal, J. T. ^{[25
]}

Chomienne, C. ^{[26
]}

Kiladjian, J. J. ^{[27
,28
]}

Barbui, T. ^{[29
]}

Grimwade, D. ^{[1
]}

机构：

[1] Kings Coll London, Sch Med, Canc Genet Lab, Dept Med & Mol Genet, London SE1 9RT, England

[2] GSTS Pathol, Mol Oncol Diagnost Unit, London, England

[3] Univ Florence, Dept Expt & Clin Med, Florence, Italy

[4] Ctr Hosp Univ, Hematol Lab, Bordeaux, France

[5] Univ Hosp, Dept Hematol, Bern, Switzerland

[6] Univ Bern, Bern, Switzerland

[7] Hop St Louis, AP HP, Unite Biol Cellulaire, Paris, France

[8] Vejle Sygehus, Klinisk Biokemi, Vejle, Denmark

[9] Qiagen Marseille, Marseille, France

[10] Univ Nantes, INSERM, U892, Ctr Hosp Univ, Nantes, France

[11] Radboud Univ Nijmegen, Med Ctr, Hematol Lab, Dept Lab Med, NL-6525 ED Nijmegen, Netherlands

[12] Munich Leukemia Lab, Munich, Germany

[13] Addenbrookes Hosp, Mol Malignancy Lab, Cambridge, England

[14] Addenbrookes Hosp, Haematooncol Diagnost Serv, Cambridge, England

[15] Guys & St Thomas NHS Fdn Trust, Dept Histopathol, London, England

[16] Kings Coll Hosp London, Dept Haematol, London, England

[17] West Midlands Reg Genet Lab, Birmingham, W Midlands, England

[18] Wessex Reg Genet Lab, Salisbury, Wilts, England

[19] Belfast City Hosp, Dept Hematol, Belfast BT9 7AD, Antrim, North Ireland

[20] Univ Hosp Freiburg, Dept Mol Hematol, Freiburg, Germany

[21] Univ Utah, Dept Pathol, Salt Lake City, UT USA

[22] ARUP Labs, Salt Lake City, UT USA

[23] Queens Univ Belfast, Belfast, Antrim, North Ireland

[24] Guys & St Thomas NHS Fdn Trust, Dept Haematol, London, England

[25] Univ Utah, Sch Med, Div Hematol, MPD Res Consortium, Salt Lake City, UT USA

[26] Inst Univ Hematol, INSERM, UMR S940, Paris, France

[27] Hop St Louis, Clin Invest Ctr, Paris, France

[28] French Intergrp Myeloproliferat Disorders FIM, Paris, France

[29] Osped Riuniti Bergamo, I-24100 Bergamo, Italy

来源：

LEUKEMIA | 2013年 / 27卷 / 10期

关键词：

JAK2-V617F; qPCR standardization; MRD; STEM-CELL TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; DONOR-LYMPHOCYTE INFUSION; JAK2V617F ALLELE BURDEN; TYROSINE KINASE JAK2; POLYCYTHEMIA-VERA; PRIMARY MYELOFIBROSIS; MYELOID METAPLASIA; MOLECULAR DIAGNOSIS; V617F MUTATION;

D O I：

10.1038/leu.2013.219

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Reliable detection of JAK2-V617F is critical for accurate diagnosis of myeloproliferative neoplasms (MPNs); in addition, sensitive mutation-specific assays can be applied to monitor disease response. However, there has been no consistent approach to JAK2-V617F detection, with assays varying markedly in performance, affecting clinical utility. Therefore, we established a network of 12 laboratories from seven countries to systematically evaluate nine different DNA-based quantitative PCR (qPCR) assays, including those in widespread clinical use. Seven quality control rounds involving over 21 500 qPCR reactions were undertaken using centrally distributed cell line dilutions and plasmid controls. The two best-performing assays were tested on normal blood samples (n = 100) to evaluate assay specificity, followed by analysis of serial samples from 28 patients transplanted for JAK2-V617F-positive disease. The most sensitive assay, which performed consistently across a range of qPCR platforms, predicted outcome following transplant, with the mutant allele detected a median of 22 weeks (range 6-85 weeks) before relapse. Four of seven patients achieved molecular remission following donor lymphocyte infusion, indicative of a graft vs MPN effect. This study has established a robust, reliable assay for sensitive JAK2-V617F detection, suitable for assessing response in clinical trials, predicting outcome and guiding management of patients undergoing allogeneic transplant.

引用

页码：2032 / 2039

页数：8

共 54 条

[1] Impact of JAK2V617F mutation status, allele burden, and clearance after allogeneic stem cell transplantation for myelofibrosis [J].

Alchalby, Haefaa ;

Badbaran, Anita ;

Zabelina, Tatjana ;

Kobbe, Guido ;

Hahn, Joachim ;

Wolff, Daniel ;

Bornhaeuser, Martin ;

Thiede, Christian ;

Baurmann, Herrad ;

Bethge, Wolfgang ;

Hildebrandt, York ;

Bacher, Ulrike ;

Fehse, Boris ;

Zander, Axel R. ;

Kroeger, Nicolaus .

BLOOD, 2010, 116 (18) :3572-3581

[2] Imetelstat Rapidly Induces and Maintains Substantial Hematologic and Molecular Responses in Patients with Essential Thrombocythemia (ET) Who Are Refractory or Intolerant to Prior Therapy: Preliminary Phase II Results [J].

Baerlocher, Gabriela M. ;

Leibundgut, Elisabeth Oppliger ;

Ayran, Christina ;

Blaney, Martha ;

Burington, Bart ;

Morfeld, Dianne ;

Odenike, Olatoyosi ;

Ottman, Oliver ;

Reddy, Anita ;

Roeth, Alexander ;

Spitzer, Gary ;

Stuart, Monic J. ;

Verstovsek, Srdan ;

Snyder, David S. .

BLOOD, 2012, 120 (21)

[3] JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis [J].

Barosi, Giovanni ;

Bergamaschi, Gaetano ;

Marchetti, Monia ;

Vannucchi, Alessandro M. ;

Guglielmelli, Paola ;

Antonioli, Elisabetta ;

Massa, Margherita ;

Rosti, Vittorio ;

Campanelli, Rita ;

Villani, Laura ;

Viarengo, Gianluca ;

Gattoni, Elisabetta ;

Gerli, Giancarla ;

Specchia, Giorgina ;

Tinelli, Carmine ;

Rambaldi, Alessandro ;

Barbui, Tiziano .

BLOOD, 2007, 110 (12) :4030-4036

[4] Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders [J].

Baxter, EJ ;

Scott, LM ;

Campbell, PJ ;

East, C ;

Fourouclas, N ;

Swanton, S ;

Vassiliou, GS ;

Bench, AJ ;

Boyd, EM ;

Curtin, N ;

Scott, MA ;

Erber, WN ;

Green, AR .

LANCET, 2005, 365 (9464) :1054-1061

[5] The role of molecular genetic analysis within the diagnostic haemato-oncology laboratory [J].

Bench, A. J. .

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, 2012, 34 (01) :21-34

[6] Molecular diagnosis of the myeloproliferative neoplasms: UK guidelines for the detection of JAK2 V617F and other relevant mutations [J].

Bench, Anthony J. ;

White, Helen E. ;

Foroni, Letizia ;

Godfrey, Anna L. ;

Gerrard, Gareth ;

Akiki, Susanna ;

Awan, Abida ;

Carter, Ian ;

Goday-Fernandez, Andrea ;

Langabeer, Stephen E. ;

Clench, Tim ;

Clark, Jordan ;

Evans, Paul A. ;

Grimwade, David ;

Schuh, Anna ;

McMullin, Mary F. ;

Green, Anthony R. ;

Harrison, Claire N. ;

Cross, Nicholas C. P. .

BRITISH JOURNAL OF HAEMATOLOGY, 2013, 160 (01) :25-34

[7] Relapse of postpolycythemia myelofibrosis after allogeneic stem cell transplantation in a polycythemic phase: successful treatment with donor lymphocyte infusion directed by quantitative PCR test for V617F-JAK2 mutation [J].

Benjamini, O. ;

Koren-Michowitz, M. ;

Amariglio, N. ;

Kroger, N. ;

Nagler, A. ;

Shimoni, A. .

LEUKEMIA, 2008, 22 (10) :1961-1963

[8] Genetic and Epigenetic Complexity in Myeloproliferative Neoplasms [J].

Cross, Nicholas C. P. .

HEMATOLOGY-AMERICAN SOCIETY HEMATOLOGY EDUCATION PROGRAM, 2011, :208-214

[9] Donor lymphocyte infusions for relapse of chronic myeloid leukemia after allogeneic stem cell transplant: Where we now stand [J].

Dazzi, F ;

Szydlo, RM ;

Goldman, JM .

EXPERIMENTAL HEMATOLOGY, 1999, 27 (10) :1477-1486

[10] Influence of the JAK2 V617F mutation and inherited thrombophilia on the thrombotic risk among patients with essential thrombocythemia [J].

De Stefano, Valerio ;

Za, Tommaso ;

Rossi, Elena ;

Fiorini, Alessia ;

Ciminello, Angela ;

Luzzi, Claudia ;

Chiusolo, Patrizia ;

Sica, Simona ;

Leone, Giuseppe .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2009, 94 (05) :733-737

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