This table lists Jak and cytokine receptor mutations found in various cancers, along with the corresponding publication.

Jak Mutants

Jak Mutants Cytokine Receptor Disease References
Jak2 V617F EpoR, TpoR (MPL), G-CSFR Myeloproliferative neoplasms (MNPs), PV, ET, PMF (1, 2, 3, 4, 5)
Jak2 K539L / exon 12 mutants EpoR MNP: PV (6)
Jak2 T875N undetermined AML (AMKL) (7)
Jak3 A572V undetermined AML (AMKL) (cell lines) (8)
Jak1 V658F / Jak1 A634D / R879H / R724S IL2R, IL9R, other undetermined T-ALL (9, 10)
Jak1 R683G/S Jak2 DIREED TLSPR Pediatric and Down syndrome ALL (11, 12, 13, 14, 15)

Receptor Mutants

Receptor Mutants Cytokine Receptor Disease References
TpoR W515L/K/A Jak2 MPNs: ET, PMF (16, 17, 18)
TpoR S505N     (19)
TpoR S487A     (20)
TLSPR F232S / TLSPR translocations Jak2 R683 mutants Pediatric and Down syndrome ALL (13, 21, 22, 23)

We would like to thank Prof. Stefan N. Constantinescu, Ludwig Institute for Cancer Research, Brussels, Belgium, for contributing to this table.

References

  1. James C, Ugo V, Le Couédic JP, Staerk J, Delhommeau F, Lacout C, Garçon L, Raslova H, Berger R, Bennaceur-Griscelli A, Villeval JL, Constantinescu SN, Casadevall N, Vainchenker W (2005) A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 434(7037), 1144–8.
  2. 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 (2005) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365(9464), 1054–61.
  3. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, Tichelli A, Cazzola M, Skoda RC (2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders. N. Engl. J. Med. 352(17), 1779–90.
  4. Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ, Boggon TJ, Wlodarska I, Clark JJ, Moore S, Adelsperger J, Koo S, Lee JC, Gabriel S, Mercher T, D'Andrea A, Fröhling S, Döhner K, Marynen P, Vandenberghe P, Mesa RA, Tefferi A, Griffin JD, Eck MJ, Sellers WR, Meyerson M, Golub TR, Lee SJ, Gilliland DG (2005) Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 7(4), 387–97.
  5. Vainchenker W, Dusa A, Constantinescu SN (2008) JAKs in pathology: role of Janus kinases in hematopoietic malignancies and immunodeficiencies. Semin. Cell Dev. Biol. 19(4), 385–93.
  6. Scott LM, Tong W, Levine RL, Scott MA, Beer PA, Stratton MR, Futreal PA, Erber WN, McMullin MF, Harrison CN, Warren AJ, Gilliland DG, Lodish HF, Green AR (2007) JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N. Engl. J. Med. 356(5), 459–68.
  7. Mercher T, Wernig G, Moore SA, Levine RL, Gu TL, Fröhling S, Cullen D, Polakiewicz RD, Bernard OA, Boggon TJ, Lee BH, Gilliland DG (2006) JAK2T875N is a novel activating mutation that results in myeloproliferative disease with features of megakaryoblastic leukemia in a murine bone marrow transplantation model. Blood 108(8), 2770–9.
  8. Walters DK, Mercher T, Gu TL, O'Hare T, Tyner JW, Loriaux M, Goss VL, Lee KA, Eide CA, Wong MJ, Stoffregen EP, McGreevey L, Nardone J, Moore SA, Crispino J, Boggon TJ, Heinrich MC, Deininger MW, Polakiewicz RD, Gilliland DG, Druker BJ (2006) Activating alleles of JAK3 in acute megakaryoblastic leukemia. Cancer Cell 10(1), 65–75.
  9. Flex E, Petrangeli V, Stella L, Chiaretti S, Hornakova T, Knoops L, Ariola C, Fodale V, Clappier E, Paoloni F, Martinelli S, Fragale A, Sanchez M, Tavolaro S, Messina M, Cazzaniga G, Camera A, Pizzolo G, Tornesello A, Vignetti M, Battistini A, Cavé H, Gelb BD, Renauld JC, Biondi A, Constantinescu SN, Foà R, Tartaglia M (2008) Somatically acquired JAK1 mutations in adult acute lymphoblastic leukemia. J. Exp. Med. 205(4), 751–8.
  10. Jeong EG, Kim MS, Nam HK, Min CK, Lee S, Chung YJ, Yoo NJ, Lee SH (2008) Somatic mutations of JAK1 and JAK3 in acute leukemias and solid cancers. Clin. Cancer Res. 14(12), 3716–21.
  11. Malinge S, Ben-Abdelali R, Settegrana C, Radford-Weiss I, Debre M, Beldjord K, Macintyre EA, Villeval JL, Vainchenker W, Berger R, Bernard OA, Delabesse E, Penard-Lacronique V (2007) Novel activating JAK2 mutation in a patient with Down syndrome and B-cell precursor acute lymphoblastic leukemia. Blood 109(5), 2202–4.
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  13. Mullighan CG, Collins-Underwood JR, Phillips LA, Loudin MG, Liu W, Zhang J, Ma J, Coustan-Smith E, Harvey RC, Willman CL, Mikhail FM, Meyer J, Carroll AJ, Williams RT, Cheng J, Heerema NA, Basso G, Pession A, Pui CH, Raimondi SC, Hunger SP, Downing JR, Carroll WL, Rabin KR (2009) Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia. Nat. Genet. 41(11), 1243–6.
  14. Bercovich D, Ganmore I, Scott LM, Wainreb G, Birger Y, Elimelech A, Shochat C, Cazzaniga G, Biondi A, Basso G, Cario G, Schrappe M, Stanulla M, Strehl S, Haas OA, Mann G, Binder V, Borkhardt A, Kempski H, Trka J, Bielorei B, Avigad S, Stark B, Smith O, Dastugue N, Bourquin JP, Tal NB, Green AR, Izraeli S (2008) Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down's syndrome. Lancet 372(9648), 1484–92.
  15. Kearney L, Gonzalez De Castro D, Yeung J, Procter J, Horsley SW, Eguchi-Ishimae M, Bateman CM, Anderson K, Chaplin T, Young BD, Harrison CJ, Kempski H, So CW, Ford AM, Greaves M (2009) Specific JAK2 mutation (JAK2R683) and multiple gene deletions in Down syndrome acute lymphoblastic leukemia. Blood 113(3), 646–8.
  16. Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M, Cuker A, Wernig G, Moore S, Galinsky I, DeAngelo DJ, Clark JJ, Lee SJ, Golub TR, Wadleigh M, Gilliland DG, Levine RL (2006) MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 3(7), e270.
  17. Pardanani AD, Levine RL, Lasho T, Pikman Y, Mesa RA, Wadleigh M, Steensma DP, Elliott MA, Wolanskyj AP, Hogan WJ, McClure RF, Litzow MR, Gilliland DG, Tefferi A (2006) MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 108(10), 3472–6.
  18. Pecquet C, Staerk J, Chaligné R, Goss V, Lee KA, Zhang X, Rush J, Van Hees J, Poirel HA, Scheiff JM, Vainchenker W, Giraudier S, Polakiewicz RD, Constantinescu SN (2010) Induction of myeloproliferative disorder and myelofibrosis by thrombopoietin receptor W515 mutants is mediated by cytosolic tyrosine 112 of the receptor. Blood 115(5), 1037–48.
  19. Ding J, Komatsu H, Wakita A, Kato-Uranishi M, Ito M, Satoh A, Tsuboi K, Nitta M, Miyazaki H, Iida S, Ueda R (2004) Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin. Blood 103(11), 4198–200.
  20. Malinge S, Ragu C, Della-Valle V, Pisani D, Constantinescu SN, Perez C, Villeval JL, Reinhardt D, Landman-Parker J, Michaux L, Dastugue N, Baruchel A, Vainchenker W, Bourquin JP, Penard-Lacronique V, Bernard OA (2008) Activating mutations in human acute megakaryoblastic leukemia. Blood 112(10), 4220–6.
  21. Russell LJ, Capasso M, Vater I, Akasaka T, Bernard OA, Calasanz MJ, Chandrasekaran T, Chapiro E, Gesk S, Griffiths M, Guttery DS, Haferlach C, Harder L, Heidenreich O, Irving J, Kearney L, Nguyen-Khac F, Machado L, Minto L, Majid A, Moorman AV, Morrison H, Rand V, Strefford JC, Schwab C, Tönnies H, Dyer MJ, Siebert R, Harrison CJ (2009) Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia. Blood 114(13), 2688–98.
  22. Chapiro E, Russell L, Lainey E, Kaltenbach S, Ragu C, Della-Valle V, Hanssens K, Macintyre EA, Radford-Weiss I, Delabesse E, Cavé H, Mercher T, Harrison CJ, Nguyen-Khac F, Dubreuil P, Bernard OA (2010) Activating mutation in the TSLPR gene in B-cell precursor lymphoblastic leukemia. Leukemia 24(3), 642–5.
  23. Hertzberg L, Vendramini E, Ganmore I, Cazzaniga G, Schmitz M, Chalker J, Shiloh R, Iacobucci I, Shochat C, Zeligson S, Cario G, Stanulla M, Strehl S, Russell LJ, Harrison CJ, Bornhauser B, Yoda A, Rechavi G, Bercovich D, Borkhardt A, Kempski H, te Kronnie G, Bourquin JP, Domany E, Izraeli S (2010) Down syndrome acute lymphoblastic leukemia, a highly heterogeneous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the International BFM Study Group. Blood 115(5), 1006–17.

created November 2010