title: Imatinib and tyrosine kinase inhibition, in the management of BCR-ABL negative myeloproliferative disorders.
abstract: The chronic myeloproliferative disorders (MPDs) include the spectrum of clonal hematopoietic stem cell disorders whose phenotype derive from the primary cell expanded in a proliferative state. The MPDs (which include polycythemia vera (PV), essential thrombocythemia (ET), chronic eosinophilic leukemia (CEL), primary myelofibrosis (PMF), chronic myelomonocytic leukemia (CMML), and systemic mast cell disease (SMCD)) exclude chronic myeloid leukemia (CML) because of the pathognomic importance of the BCR-ABL translocation for the diagnosis and treatment of this disorder with imatinib mesylate. Empiric use of imatinib mesylate against the spectrum of BCR-ABL negative MPDs has had mixed results. Significant benefits were obtained when empiric use of imatinib in CEL and CMML led to significant clinical benefit and the discovery of the role of rearrangements of the platelet derived growth factor receptor -alpha (PDGFRa-FIP1L1 in CEL and SMCD) and -beta (PDGFRb through TEL-PDGFRb) for CMML). Empiric use of imatinib in PMF has been disappointing, and in PV quite modest. Although next generation Abelson kinase inhibitors such as dasatinib or nilotinib may expand the role for these agents in MPDs, targeted inhibition of the mutant kinase JAK2(V617F) is more likely to make significant therapeutic gains in the classic MPDs of PV, ET, and PMF.
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Ruben A
authors.initials: RA
authors.lastname: Mesa
references.citation: Blood. 2005 Apr 1;105(7):2664-70
references.pmid: 15585653
references.citation: Mayo Clin Proc. 2006 Apr;81(4):553-63
references.pmid: 16610578
references.citation: N Engl J Med. 2004 Jan 8;350(2):114-24
references.pmid: 14711910
references.citation: Lancet. 2003 Aug 16;362(9383):535-6
references.pmid: 12932387
references.citation: Am J Med. 2004 Nov 15;117(10):755-61
references.pmid: 15541325
references.citation: Nat Med. 1996 May;2(5):561-6
references.pmid: 8616716
references.citation: Histol Histopathol. 2004 Oct;19(4):1245-60
references.pmid: 15375769
references.citation: Eur J Haematol. 2001 Jan;66(1):37-42
references.pmid: 11168506
references.citation: Mayo Clin Proc. 1998 Dec;73(12):1177-84
references.pmid: 9868417
references.citation: Blood. 2002 Mar 15;99(6):2255-8
references.pmid: 11877308
references.citation: PLoS Med. 2006 Jul;3(7):e270
references.pmid: 16834459
references.citation: N Engl J Med. 2003 Mar 27;348(13):1201-14
references.pmid: 12660384
references.citation: Br J Haematol. 2005 Mar;128(5):690-7
references.pmid: 15725091
references.citation: Lancet. 2005 Mar 19-25;365(9464):1054-61
references.pmid: 15781101
references.citation: Blood. 1996 Aug 1;88(3):1013-8
references.pmid: 8704209
references.citation: Br J Cancer. 2006 Jun 19;94(12):1765-9
references.pmid: 16721371
references.citation: Nature. 2005 Apr 28;434(7037):1144-8
references.pmid: 15793561
references.citation: Br J Haematol. 2004 Nov;127(4):399-403
references.pmid: 15521916
references.citation: N Engl J Med. 1995 Apr 27;332(17):1132-6
references.pmid: 7700286
references.citation: Br J Haematol. 2005 Nov;131(3):320-8
references.pmid: 16225651
references.citation: Leuk Res. 2006 Nov;30(11):1457-60
references.pmid: 16563504
references.citation: Eur J Haematol. 1990 Jan;44(1):33-8
references.pmid: 2307218
references.citation: Blood. 2000 Nov 15;96(10):3374-80
references.pmid: 11071630
references.citation: N Engl J Med. 2002 Feb 28;346(9):645-52
references.pmid: 11870241
references.citation: Pathol Biol (Paris). 2001 Mar;49(2):148-52
references.pmid: 11317960
references.citation: Blood. 2006 Sep 1;108(5):1478-84
references.pmid: 16627756
references.citation: Haematologica. 2000 Jun;85(6):595-9
references.pmid: 10870115
references.citation: Cancer. 2003 Jun 1;97(11):2760-6
references.pmid: 12767088
references.citation: N Engl J Med. 2002 Feb 28;346(9):712-3
references.pmid: 11870257
references.citation: Cancer Cell. 2005 Apr;7(4):387-97
references.pmid: 15837627
references.citation: Blood. 1999 May 1;93(9):2831-8
references.pmid: 10216077
references.citation: Blood. 2007 Jul 1;110(1):375-9
references.pmid: 17363731
references.citation: Blood. 2003 Dec 1;102(12):3912-8
references.pmid: 12920019
references.citation: N Engl J Med. 2002 Aug 15;347(7):481-7
references.pmid: 12181402
references.citation: Blood. 1998 Jun 15;91(12):4419-26
references.pmid: 9616134
references.citation: J Natl Cancer Inst. 1960 Jul;25:85-109
references.pmid: 14427847
references.citation: Eur J Haematol. 2005 Feb;74(2):117-20
references.pmid: 15654901
references.citation: N Engl J Med. 2005 Jul 7;353(1):33-45
references.pmid: 16000354
references.citation: Br J Haematol. 2006 Jun;133(5):468-92
references.pmid: 16681635
references.citation: Blood. 2006 Nov 15;108(10):3472-6
references.pmid: 16868251
references.citation: Chest. 2001 Sep;120(3):801-8
references.pmid: 11555513
references.citation: Am J Hematol. 1999 May;61(1):10-5
references.pmid: 10331505
references.citation: Br J Haematol. 1997 Sep;98(4):1004-9
references.pmid: 9326204
references.citation: Leukemia. 2006 May;20(5):827-32
references.pmid: 16498388
references.citation: N Engl J Med. 2007 Feb 1;356(5):459-68
references.pmid: 17267906
references.citation: Blood. 2003 May 1;101(9):3391-7
references.pmid: 12506022
references.citation: Leuk Res. 2006 Aug;30(8):965-70
references.pmid: 16406016
references.citation: Blood. 2005 May 15;105(10):4115-9
references.pmid: 15671439
references.citation: Mayo Clin Proc. 2006 Feb;81(2):159-66
references.pmid: 16471068
references.citation: Blood. 2003 Jun 15;101(12):4714-6
references.pmid: 12595304
references.citation: Br J Haematol. 2002 Mar;116(3):576-81
references.pmid: 11849213
references.citation: J Biol Chem. 2007 Feb 9;282(6):3428-32
references.pmid: 17178722
references.citation: Blood. 2000 Apr 1;95(7):2226-33
references.pmid: 10733489
references.citation: Am J Med Sci. 1988 May;295(5):472-6
references.pmid: 3376991
references.citation: Br J Haematol. 2006 Nov;135(3):303-16
references.pmid: 16956345
references.citation: Lancet. 2002 May 4;359(9317):1577-8
references.pmid: 12047970
references.citation: N Engl J Med. 2001 Apr 5;344(14):1031-7
references.pmid: 11287972
references.citation: J Med Chem. 2004 Dec 30;47(27):6658-61
references.pmid: 15615512
references.citation: Blood. 2005 Nov 1;106(9):3206-13
references.pmid: 16030188
references.citation: Curr Hematol Rep. 2003 May;2(3):264-70
references.pmid: 12901349
references.citation: Semin Thromb Hemost. 1997;23(4):357-63
references.pmid: 9263352
references.citation: Blood. 2002 May 15;99(10):3854-6
references.pmid: 11986248
references.citation: Leuk Res. 2007 Jun;31(6):737-40
references.pmid: 17210175
references.citation: Exp Hematol. 2005 May;33(5):523-30
references.pmid: 15850829
references.citation: Blood. 1951 Apr;6(4):372-5
references.pmid: 14820991
references.citation: Curr Opin Hematol. 1998 Sep;5(5):327-31
references.pmid: 9776211
references.citation: Br J Haematol. 2001 Jun;113(3):763-71
references.pmid: 11380468
references.citation: N Engl J Med. 2005 Apr 28;352(17):1779-90
references.pmid: 15858187