JAK2 V617F in myeloid disorders: Molecular diagnostic techniques and their clinical utility: A paper from the 2005 William Beaumont Hospital Symposium on Molecular Pathology

Journal of Molecular Diagnostics

Volumn 8, Issue 4, 2006, Pages 397-411

  Steensma, David P ^a  

^a Mayo Clinic   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; DNA POLYMERASE; ERYTHROPOIETIN; GENOMIC DNA; JANUS KINASE 2; SINGLE STRANDED DNA;

ACUTE GRANULOCYTIC LEUKEMIA; ALLELE; BONE MARROW DISEASE; BUDD CHIARI SYNDROME; DIAGNOSTIC ACCURACY; DIAGNOSTIC PROCEDURE; DIAGNOSTIC TEST; DIAGNOSTIC VALUE; DNA DENATURATION; DNA HYBRIDIZATION; DNA SEQUENCE; DNA TEMPLATE; ERYTHROCYTOSIS; GENOTYPE; HUMAN; MUTATIONAL ANALYSIS; MYELODYSPLASTIC SYNDROME; MYELOID PROGENITOR CELL; MYELOPROLIFERATIVE DISORDER; NUCLEIC ACID BASE SUBSTITUTION; NUCLEOTIDE SEQUENCE; POINT MUTATION; REAL TIME POLYMERASE CHAIN REACTION; RESTRICTION FRAGMENT LENGTH POLYMORPHISM; REVIEW; THROMBOCYTOSIS;

EID: 33748592820     PISSN: 15251578     EISSN: None     Source Type: Journal    
DOI: 10.2353/jmoldx.2006.060007     Document Type: Review

References (90)

1. James C, Ugo V, Le Couedic J-P, Staerk J, Delhommeau F, Lacout C, Garcon L. Raslova H, Berger R, Bennaceur-Griscelli A, Villeval JL, Constantinescu SN, Casadevall N, Vainchenker W: A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005, 434:1144-1148
2. Kralovics R, Passamonti F, Buser AS, Teo S-S, Tiedt R, Passweg JR, Ticheli A, Cazzola M, Skoda RC: A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005, 352:1779-1790
3. Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJP, Boggon TJ, Wlodarska I, Clark JJ, Moore S, Adelsperger J, Koo S, Lee JC, Gabriel S, Mercher T, D'Andrea A, Frohling S, Dohner K, Marynen P, Vandenberghe P, Mesa RA, Tefferi A, Griffin JD, Eck MJ, Sellers WR, Meyerson M, Golub TR, Lee SJ, Gilliland DG: Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 2005, 7:387-397
4. 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: Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. The Lancet 2005, 365:1054-1061
5. Zhao, R, Xing S, Li Z, Fu X, Li Q, Krantz SB, Zhao ZJ: Identification of an acquired JAK2 mutation in Polycythemia vera. J Biol Chem 2005, 280:22788-22792
6. Reilly JT: Receptor tyrosine kinases in normal and malignant haematopoiesis. Blood Rev 2003, 17:241-248
7. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S, Sawyers CL: Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001, 344:1031-1037
8. Hannah AL: Kinases as drug discovery targets in hematologic malignancies. Curr Mol Med 2005, 5:625-642
9. den Dunnen JT, Antonarakis SE: Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat 2000, 15:7-12
10. Nelson ME, Steensma DP: JAK2 V617F in myeloid disorders: what do we know now, and where are we headed? Leuk Lymphoma 2006, 47:177-194
11. De Keersmaecker K, Cools J: Chronic myeloproliferative disorders: a tyrosine kinase tale. Leukemia 2005, 20:200-205
12. Kaushansky K: On the molecular origins of the chronic myeloproliferative disorders: it all makes sense. Blood 2005, 105:4187-4190
13. Tefferi A, Gilliland DG: The JAK2V617F tyrosine kinase mutation in myeloproliferative disorders: status report and immediate implications for disease classification and diagnosis. Mayo Clin Proc 2005, 80:947-958
14. Jaffe ES, Harris NL, Stein H, Vardiman JW (Eds): World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Hematopoietic and Lymphoid Tissues. Lyon, France, IARC Press, 2001
15. Vardiman JW, Harris NL, Brunning RD: The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002, 100:2292-2302
16. Pearson TC, Messinezy M: The diagnostic criteria of polycythaemia rubra vera. Leuk Lymphoma 1996, 22(Suppl 1):87-93
17. James C, Delhommeau F, Marzac C, Teyssandier I, Couedic JP, Giraudier S, Roy L, Saulnier P, Lacroix L, Maury S, Tulliez M, Vainchenker W, Ugo V, Casadevall N: Detection of JAK2 V617F as a first intention diagnostic test for erythrocytosis. Leukemia 2006, 20:350-353
18. James C, Ugo V, Casadevall N, Constantinescu SN, Vainchenker W: A JAK2 mutation in myeloproliferative disorders: pathogenesis and therapeutic and scientific prospects. Trends Mol Med 2005, 11:546-554
19. Steensma DP, Dewald GW, Lasho TL, Powell HL, McClure RF, Levine RL, Gilliland DG, Tefferi A: The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both "atypical" myeloproliferative disorders and myelodysplastic syndromes. Blood 2005, 106:1207-1209
20. Levine RL, Loriaux M, Huntly BJ, Loh ML, Beran M, Stoffregen E, Berger R, Clark JJ, Willis SG, Nguyen KT, Flores NJ, Estey E, Gattermann N, Armstrong S, Look AT, Griffin JD, Bernard OA, Heinrich MC, Gilliland DG, Druker B, Deininger MWN: The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia. Blood 2005, 106:3377-3379
21. Jelinek J, Oki Y, Gharibyan V, Bueso-Ramos C, Prchal JT, Verstovsek S, Beran M, Estey E, Kantarjian HM, Issa JP: JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome-negative CML, and megakaryocytic leukemia. Blood 2005, 106:3370-3373
22. Lee JW, Kim YG, Soung YH, Han KJ, Kim SY, Rhim HS, Min WS, Nam SW, Park WS, Lee JY, Yoo NJ, Lee SH: The JAK2 V617F mutation in de novo acute myelogenous leukemias. Oncogene 2006, 25:1434-1436
23. Frohling S, Lipka DB, Kayser S, Scholl C, Schlenk RF, Dohner H, Gilliland DG, Levine RL, Dohner K: Rare occurrence of the JAK2 V617F mutation in AML subtypes M5, M6, and M7. Blood 2006, 107:1242-1243
24. Jones AV, Kreil S, Zoi K, Waghorn K, Curtis C, Zhang L, Score J, Seear R, Chase AJ, Grand FH, White H, Zoi C, Loukopoulos D, Terpos E, Vervessou EC, Schultheis B, Emig M, Ernst T, Lengfelder E, Hehlmann R, Hochhaus A, Oscier D, Silver RT, Reiter A, Cross NC: Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood 2005, 106:2162-2168
25. McLornan DP, Percy MJ, Jones AV, Cross NC, Vic Mullin MF: Chronic neutrophilic leukemia with an associated V617F JAK2 tyrosine kinase mutation. Haematologica 2005, 90:1696-1697
26. Tono C, Xu G, Toki T, Takahashi Y, Sasaki S, Terui K, Ito E: JAK2 Va1617Phe activating tyrosine kinase mutation in juvenile myelomonocytic leukemia. Leukemia 2005, 19:1843-1844
27. Ohyashiki K, Aota Y, Akahane D, Gotoh A, Miyazawa K, Kimura Y, Ohyashiki JH: The JAK2 V617F tyrosine kinase mutation in myelodysplastic syndromes (MDS) developing myelofibrosis indicates the myeloproliferative nature in a subset of MDS patients. Leukemia 2005, 19:2359-2360
28. Szpurka H, Tiu R, Hsi E, Lichtin AE, Sekeres MA, Theil KS, Maciejewski JP: Presence of JAK2 mutations in MDS/MPD-u WHO classified patients and not other forms of MDS suggests their derivation from classical myeloproliferative syndrome (Abstract 369). Blood 2005, 106:112a
29. Shaw GR: Ringed sideroblasts with thrombocytosis: an uncommon mixed myelodysplastic/myeloproliferative disease of older adults. Br J Haematol 2005, 131:180-184
30. McClure R, Mai M, Lasho T: Validation of two clinically useful assays for evaluation of JAK2 V617F mutation in chronic myeloproliferative disorders. Leukemia 2006, 20:168-171
31. Bellanne-Chantelot C, Labopin M, Chaumarel I, Delhommeau F, Leroy G, Bellanger F, Thomas G, Vainchenker W, Najman A: Heterogeneous distribution of the JAK2 Val617Phe activating mutation in familial myeloproliferative disorders (Abstract 115). Blood 2005, 106: 38a
32. Kratz CP, Boll S, Kontny U, Schrappe M, Niemeyer CM, Stanulla M: Mutational screen reveals a novel JAK2 mutation, L611S, in a child with acute lymphoblastic leukemia. Leukemia 2006, 20:381-383
33. Steensma DP, Dewald GW, Lasho TL, Powell HL, McClure RF, Levine RL, Gilliland DG, Tefferi A: The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both "atypical" myeloproliferative disorders and the myelodysplastic syndrome. Blood 2005, 106:1207-1209
34. Scott LM, Campbell PJ, Baxter EJ, Todd T, Stephens P, Edkins S, Wooster R, Stratton MR, Futreal PA, Green AR: The V617F JAK2 mutation is uncommon in cancers and in myeloid malignancies other than the classic myeloproliferative disorders. Blood 2005, 106:2920-2921
35. Jones AV, Kreil S, Zoi K, Waghorn K, Curtis C, Zhang L, Score J, Seear R, Chase AJ, Grand FH, White H, Zoi C, Loukopoulos D, Terpos E, Vervessou EC, Schultheis B, Emig M, Ernst T, Lengfelder E, Hehlmann R, Hochhaus A, Oscier D, Silver RT, Reiter A, Cross NC: Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood 2005, 106:2162-2168
36. Tefferi A, Lasho TL, Schwager SM, Steensma DP, Mesa RA, Li CY, Wadleigh M, Gary Gilliland D: The JAK2(V617F) tyrosine kinase mutation in myelofibrosis with myeloid metaplasia: lineage specificity and clinical correlates. Br J Haematol 2005, 131:320-328
37. Fitzgibbon J, Smith LL, Raghavan M, Smith ML, Debernardi S, Skoulakis S, Lillington D, Lister TA, Young BD: Association between acquired uniparental disomy and homozygous gene mutation in acute myeloid leukemias. Cancer Res 2005, 65:9152-9154
38. Cheung B, Radia D, Pantelidis P, Yadegarfar G, Harrison C: The presence of the JAK2 V617F mutation is associated with a higher haemoglobin and increased risk of thrombosis in essential thrombocythaemia. Br J Haematol 2006, 132:244-245
39. Campbell PJ, Scott LM, Buck G, Wheatley K, East CL, Marsden JT, Duffy A, Boyd EM, Bench AJ, Scott MA, Vassiliou GS, Milligan DW, Smith SR, Erber WN, Bareford D, Wilkins BS, Reilly JT, Harrison CN, Green AR, United Kingdom Myeloproliferative Disorders Study Group, Medical Research Council Adult Leukaemia Working Party, Australasian Leukaemia and Lymphoma Group: Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study. Lancet 2005, 366:1945-1953
40. Campbell PJ, Griesshammer M, Dohner K, Dohner H, Kusec R, Hasselbalch HC, Larsen TS, Pallisgaard N, Giraudier S, Le Bousse-Kerdiles MC, Desterke C, Guerton B, Dupriez B, Bordessoule D, Fenaux P, Kiladjan JJ, Viallard JF, Briere J, Harrison CN, Green AR, Reilly JT: The V617F mutation in JAK2 is associated with poorer survival in idiopathic myelofibrosis. Blood 2005, 107:2098-2100
41. Harrison CN: Platelets and thrombosis in myeloproliferative diseases. Hematology (Am Soc Hematol Educ Program) 2005:409-415
42. Antonioli E, Guglielmelli P, Pancrazzi A, Bogani C, Verrucci M, Ponziani V, Longo G, Bosi A, Vannucchi AM: Clinical implications of the JAK2 V617F mutation in essential thrombocythemia. Leukemia 2005, 19:1847-1849
43. Wolanskyj AP, Lasho TL, Schwager SM, McClure RF, Wadleigh M, Lee SJ, Gilliland DG, Tefferi A: JAK2 mutation in essential thrombocythaemia: clinical associations and long-term prognostic relevance. Br J Haematol 2005, 131:208-213
44. Goerttler PS, Steimle C, Marz E, Johansson PL. Andreasson B, Griesshammer M, Gisslinger H, Heimpel H, Pahl HL: The Jak2V617F mutation, PRV-1 overexpression and EEC formation define a similar cohort of MPD patients. Blood 2005, 106:2862-2864
45. Prober JM, Trainor GL, Dam RJ, Hobbs FW, Robertson CW, Zagursky RJ, Cocuzza AJ, Jensen MA, Baumeister K: A system for rapid DNA sequencing with fluorescent chain-terminating dideoxynucleotides. Science 1987, 238:336-341
46. Izmailov A, Goloubentzev D, Jin C, Sunay S, Wisco V, Yager TD: A general approach to the analysis of errors and failure modes in the base-calling function in automated fluorescent DNA sequencing. Electrophoresis 2002, 23:2720-2728
47. Smith TA. Whelan J, Parry PJ: Detection of single-base mutations in a mixed population of cells: a comparison of SSCP and direct sequencing. Genet Anal Tech Appl 1992, 9:143-145
48. Steensma DP, Higgs DR, Fisher CA, Gibbons RJ: Acquired somatic ATRX mutations in myelodysplastic syndrome associated with alpha thalassemia (ATMDS) convey a more severe hematologic phenotype than germline ATRX mutations. Blood 2004, 103:2019-2026
49. Steensma DP. Enough already of the word "robust"! Blood 103:746-747, 2004
50. Newton CR, Graham A, Heptinstall LE, Powell SJ, Summers C, Kalsheker N, Smith JC, Markham AF: Analysis of any point mutation in DNA: the amplification refractory mutation system (ARMS). Nucleic Acids Res 1989, 17:2503-2516
51. Kaltenboeck B, Wang C: Advances in real-time PCR: application to clinical laboratory diagnostics. Adv Clin Chem 2005, 40:219-259
52. Frayling IM, Monk E, Butler R: PCR-based methods for mutation detection. Molecular Diagnostics for the Clinical Laboratorian. Edited by WB Coleman, GJ Tsongalis. Totowa, NJ, Humana Press, 2006, p 65-74
53. Wabuyele MB, Farquar H, Stryjewski W, Hammer RP, Soper SA, Cheng YW, Barany F: Approaching real-time molecular diagnostics: single-pair fluorescence resonance energy transfer (spFRET) detection for the analysis of low abundant point mutations in K-ras oncogenes. J Am Chem Soc 2003, 125:6937-6945
54. Lasho TL, Mesa R. Gilliland DG, Tefferi A: Mutation studies in CD3+, CD19+ and CD34+ cell fractions in myeloproliferative disorders with homozygous JAK2(V617F) in granulocytes. Br J Haematol 2005, 130:797-799
55. Reeder TL, Bailey RJ, Dewald GW, Tefferi A: Both B and T lymphocytes may be clonally involved in myelofibrosis with myelold metaplasia. Blood 2003, 101:1981-1983
56. Spivak JL: Diagnosis of the myeloproliferative disorders: resolving phenotypic mimicry. Semin Hematol 2003, 40(Suppl 1):1-5
57. Two new agents effective in Gleevec-resistant CML. Cancer Biol Ther 2004, 3:1198-1199
58. Gilliland DG, Griffin JD: The roles of FLT3 in hematopoiesis and leukemia. Blood 2002, 100:1532-1542
59. Gotlib J, Cools J, Malone JM III, Schrier SL, Gilliland DG, Coutre SE: The FIP1L1-PDGFRalpha fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management. Blood 2004, 103:2879-2891
60. Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, Kutok J, Clark J, Ilene Galinsky I. Griffin JD, Cross NCP, Tefferi A, Malone J, Alam R, Schrier SL, Schmid J, Rose M, Vandenberghe P, Verhoef G, Boogaerts M, Wlodarska I, Kantarjian H, Marynen P, Coutre SE, Stone RD, Gilliland G: A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 2003, 348:1201-1214
61. Pardanani A, Ketterling RP. Brockman SR, Flynn HC, Paternoster SF, Shearer BM, Reeder TL, Li CY, Cross NC, Cools J, Gilliland DG, Dewald GW, Tefferi A: CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy. Blood 2003, 102:3093-3096
62. Tefferi A, Gilliland DG: The JAK2 V617F tyrosine kinase mutation in myeloproliferative disorders: status report and immediate implications for disease classification and diagnosis. Mayo Clin Proc 2005, 80:947-958
63. James C, Delhommeau F. Marzac C, Teyssandier I, Couedic JP, Giraudier S, Roy L, Saulnier P, Lacroix L, Maury S, Tulliez M, Vainchenker W, Ugo V, Casadevall N: Detection of JAK2 V617F as a first intention diagnostic test for erythrocytosis. Leukemia 2006, 20:350-353
64. Klippel S, Pahl HL: Molecular markers for the diagnosis of Philadelphia chromosome negative myeloproliferative disorders. Pathol Biol (Paris) 2004, 52:267-274
65. Kralovics R, Buser AS, Teo SS, Coers J, Tichelli A, van der Maas AP, Skoda RC: Comparison of molecular markers in a cohort of patients with chronic myeloproliferative disorders. Blood 2003, 102:1869-1871
66. Tefferi A: Diagnosing polycythemia vera: a paradigm shift. Mayo Clin Proc 1999, 74:159-162
67. Spivak JL: Polycythemia vera: myths, mechanisms, and management. Blood 2002, 100:4272-4290
68. Michiels JJ: Bone marrow histopathology and biological markers as specific clues to the differential diagnosis of essential thrombocythemia, polycythemia vera and prefibrotic or fibrotic agnogenic myeloid metaplasia. Hematol J 2004, 5:93-102
69. Sirhan S, Fairbanks VF, Tefferi A: Red cell mass and plasma volume measurements in polycythemia. Cancer 2005, 104:213-215
70. Tefferi A: The rise and fall of red cell mass measurement in polycythemia vera. Curr Hematol Rep 2005, 4:213-217
71. Solberg LA Jr: Therapeutic options for essential thrombocythemia and polycythemia vera. Semin Oncol 2002, 29(Suppl 10):10-15
72. Gordeuk VR, Stockton DW, Prchal JT: Congenital polycythemias/ erythrocytoses. Haematologica 2005, 90:109-116
73. Kralovics R, Indrak K, Stopka T, Berman BW, Prchal JF, Prchal JT: Two new EPO receptor mutations: truncated EPO receptors are most frequently associated with primary familial and congenital polycythemias. Blood 1997, 90:2057-2061
74. Messinezy M, Westwood NB, El-Hemaidi I, Marsden JT, Sherwood RS, Pearson TC: Serum erythropoietin values in erythrocytoses and in primary thrombocythaemia. Br J Haematol 2002, 117:47-53
75. Mossuz P, Girodon F, Donnard M, Latger-Cannard V, Dobo I, Boiret N, Lecron JC, Binquet C, Barro C, Hermouet S, Praloran V: Diagnostic value of serum erythropoetin level in patients with absolute erythrocytosis. Haematologica 2004,89:1194-1198
76. Levy VG, Ruskone A, Baillou C, Theirman-Duffaud D, Najman A, Boffa GA: Polycythemia and the Budd-Chiari syndrome: study of serum erythropoietin and bone marrow erythroid progenitors. Hepatology 1985, 5:858-861
77. Thurmes PJ, Steensma DP. Elevated erythropoietin levels in polycythemia vera: diagnostic algorithms revisited (Abstract 4964). Blood 2005, 106:321-322b
78. Messinezy M, Westwood NB, Woodcock SP, Strong RM, Pearson TC: Low serum erythropoietin: a strong diagnostic criterion of primary polycythaemia even at normal haemoglobin levels. Clin Lab Haematol 1995, 17:217-220
79. Prchal JT: Pathogenetic mechanisms of polycythemia vera and congenital polycythemic disorders. Semin Hematol 2001, 38(Suppl 2):10-20
80. Diez-Martin JL, Graham DL, Petitt RM, Dewald GW: Chromosome studies in 104 patients with polycythernia vera. Mayo Clin Proc 1991, 66:287-299
81. Harrison CN: Essential thrombocythaemia: challenges and evidence-based management. Br J Haematol 2005, 130:153-165
82. Steensma DP, Tefferi A: Cytogenetic and molecular genetic aspects of essential thrombocythemia. Acta Haematol 2002, 108:55-65
83. Tefferi A, Barbui T: bcr/abl-negative, classic myeloproliferative disorders: diagnosis and treatment. Mayo Clin Proc 2005, 80:1220-1232
84. Harrison CN, Gale RE, Machin SJ, Linch DC: A large proportion of patients with a diagnosis of essential thrombocythemia do not have a clonal disorder and may be at lower risk of thrombotic complications. Blood 1999, 93:417-424
85. Johan MF, Goodeve AC, Bowen DT, Frew ME, Reilly JT: JAK2 V617F mutation is uncommon in chronic myelomonocytic leukaemia. Br J Haematol 2005, 130:968
86. Lee JW, Kim YG, Soung YH, Han KJ, Kim SY, Rhim HS, Min WS, Nam SW, Park WS, Lee JY, Yoo NJ, Lee SH. The JAK2 V617F mutation in de novo acute myelogenous leukemias. Oncogene 2006, 25:1434-1436
87. Steensma DP, McClure RF, Karp JE, Tefferi A, Lasho TL, Powell HL, DeWald GW, Kaufmann SH: JAK2 V617F is rare in de novo AML, but STAT3 activation is common and remains unexplained. Leukemia 2006, 20:971-978
88. Menon KV, Shah V, Kamath PS: The Budd-Chiari syndrome. N Engl J Med 2004, 350:578-585
89. Patel RK, Lea N, Heneghan MA, Westwood N, Milojkovic D, Thanigaikumar K, Yallop D, Arya R, Pagliuca A, Gaken J, Heaton NA, Mufti GJ: Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome (Abstract 2588). Blood 2005, 106:728a
90. Ding J, Komatsu H, Wakita A, Kato-Uranishi M, Ito M, Satoh A, Tsuboi K, Nitta M, Miyazaki H, Iida S, Ueda R: Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin. Blood 2004, 103:4198-4200