T of tyrosine kinase inhibitor (TKI) therapy in cases with JAK
T of tyrosine kinase inhibitor (TKI) therapy in cases with JAK2 mutations and translocations is still unclear and likely ineffective in the few cases reported with translocations. However, in this case,Imatinib therapy was initiated during the second encounter (two years post-diagnosis). Loss to follow-up for the following five years precludes any conclusions regarding the effect, or lack thereof, of Imatinib in this patient. This report, complemented by data from previous cases, strongly suggests shared pathways between JAK2 activation and oncogenic events resulting in ALL, CML and probably additional lympho- and myeloproliferative disorders. This makes it imperative to utilize multiple diagnostic tools (chromosomes, FISH, etc.,) to adequately investigate hematologic malignancies. Identification of additional cases will provide the opportunity to draw more explicit genotype-phenotype correlations and implement beneficial therapeutic regimens.Consent to publish Written informed consent was obtained from the patient for publication of this Case report.Competing interests The author(s) declare that they have no competing interests. Author details 1 Cytogenetics, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA 92675, USA. 2Memorial Hermann Memorial City Medical Center, Houston, TX 77024, USA. Authors’ contributions MME, RR, SA, IZ and AL contributed to conception and design, acquisition of data, analysis and interpretation of data. RR, IZ, AL were involved in the clinical evaluation, management and long-term follow-up. MME, TS, AG, WM and SA were responsible for the pathological, cytogenetic and molecular analysis of data and results. MME and TS were involved in the manuscript preparation and finalization. All authors read and approved the final manuscript. Received: 25 January 2012 Accepted: 13 April 2012 Published: 1 May 2012 References 1. SC144 clinical trials 27107493″ title=View Abstract(s)”>PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27107493 Ihle JN: Cytokine receptor signalling. Nature 1995, 377(6550):591?94. 2. Spivak JL: Narrative review: Thrombocytosis, polycythemia vera, and JAK2 mutations: The phenotypic mimicry of chronic myeloproliferation. Ann Intern Med 2010, 152(5):300?06. 3. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, Tichelli A, Cazzola M, Skoda RC: A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005, 352(17):1779?790. 4. Lacronique V, Boureux A, Valle VD, Poirel H, Quang CT, Mauchauff^?M, Berthou C, Lessard M, Berger R, Ghysdael J, Bernard OA: A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. Science 1997, 278(5341):1309?312. 5. Neubauer H, Cumano A, M ler M, Wu H, Huffstadt U, Pfeffer K: Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis. Cell 1998, 93(3):397?09. 6. James C, Ugo V, Le Cou ic JP, Staerk J, Delhommeau F, Lacout C, Gar n 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(7037):1144?148. 7. Tefferi A, Lasho TL, Gilliland G: JAK2 mutations in myeloproliferativedisorders. N Engl J Med 2005, 353(13):1416? (author reply). 8. 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: JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 2007, 356(5):459?68.Elnaggar et a.