FLT3-mutant allelic burden and clinical status are predictive of response to FLT3 inhibitors in AML

Blood

Volumn 115, Issue 7, 2010, Pages 1425-1432

  Pratz, Keith W ^a   Sato, Takashi ^a   Murphy, Kathleen M ^a   Stine, Adam ^a   Rajkhowa, Trivikram ^a   Levis, Mark ^a  

^a JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AC 220; ANTINEOPLASTIC AGENT; CD135 ANTIGEN; KW 2449; LESTAURTINIB; MIDOSTAURIN; SORAFENIB; SUNITINIB; UNCLASSIFIED DRUG; 4'-N-BENZOYLSTAUROSPORINE; AC220 COMPOUND; BENZENESULFONIC ACID DERIVATIVE; BENZOTHIAZOLE DERIVATIVE; CARBANILAMIDE DERIVATIVE; CARBAZOLE DERIVATIVE; DRUG DERIVATIVE; FLT3 PROTEIN, HUMAN; INDAZOLE DERIVATIVE; INDOLE DERIVATIVE; PIPERAZINE DERIVATIVE; PYRIDINE DERIVATIVE; PYRROLE DERIVATIVE; STAUROSPORINE;

ACUTE GRANULOCYTIC LEUKEMIA; ADULT; AGED; ALLELE; ARTICLE; AUTOPHOSPHORYLATION; CELL DEATH; CLINICAL ARTICLE; CONTROLLED STUDY; CYTOTOXICITY; FEMALE; GENE MUTATION; HEALTH STATUS; HUMAN; HUMAN CELL; MALE; MUTANT; PREDICTION; PRIORITY JOURNAL; RELAPSE; SIGNAL TRANSDUCTION; TREATMENT RESPONSE; WILD TYPE; DRUG ANTAGONISM; DRUG EFFECT; DRUG RESISTANCE; GENETICS; MUTATION; PHOSPHORYLATION; TUMOR CELL LINE;

ALLELES; ANTINEOPLASTIC AGENTS; BENZENESULFONATES; BENZOTHIAZOLES; CARBAZOLES; CELL DEATH; CELL LINE, TUMOR; DRUG RESISTANCE, NEOPLASM; FMS-LIKE TYROSINE KINASE 3; HUMANS; INDAZOLES; INDOLES; LEUKEMIA, MYELOID, ACUTE; MUTATION; PHENYLUREA COMPOUNDS; PHOSPHORYLATION; PIPERAZINES; PYRIDINES; PYRROLES; STAUROSPORINE;

EID: 77949887020     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2009-09-242859     Document Type: Article

References (34)

1. Levis M, Small D. FLT3: ITDoes matter in leukemia. Leukemia. 2003;17(9):1738-1752.
2. Levis M, Small D. FLT3 tyrosine kinase inhibitors. Int J Hematol. 2005;82(2):100-107.
3. Knapper S. FLT3 inhibition in acute myeloid leukaemia. Br J Haematol. 2007;138(6):687-699. (Pubitemid 47313203)
4. Levis M, Smith BD, Beran M, et al. A randomized, open-label study of lestaurtinib (CEP-701), an oral FLT3 inhibitor, administered in sequence with chemotherapy in patients with relapsed AML harboring FLT3 activating mutations: clinical response correlates with successful FLT3 inhibition [abstract]. Blood. 2005;106:121a. Abstract 403.
5. Cortes J, Foran J, Devetten M, et al. Human pharmacokinetics of AC220, a potent and selective Class III receptor tyrosine kinase inhibitor [abstract]. Blood. 2007;110(11):477a. Abstract 1597.
6. Cortes J, Roboz GJ, Kantarjian H, et al. A Phase I dose escalation study of KW-2449, an oral multi-kinase inhibitor against FLT3, Abl, FGFR1 and Aurora in patients with relapsed/refractory AML, treatment resistant/intolerant CML, ALL and MDS [abstract]. Blood. 2007;110(11):277a. Abstract 909.
7. Stone RM, Fischer T, Paquette R, et al. Phase IB study of PKC412, an oral FLT3 kinase inhibitor, in sequential and simultaneous combinations with daunorubicin and cytarabine (DA) induction and high-dose cytarabine consolidation in newly diagnosed patients with AML [abstract]. Blood. 2005;106:121a. Abstract 404.
8. Ravandi F, Cortes J, Faderl S, et al. Combination of sorafenib, idarubicin, and cytarabine has a high response rate in patients with newly diagnosed acute myeloid leukemia (AML) younger than 65 years [abstract]. Blood. 2008;112:768a. Abstract 768.
9. Smith BD, Levis M, Beran M, et al. Single-agent CEP-701, a novel FLT3 inhibitor, shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemia. Blood. 2004; 103(10):3669-3676. (Pubitemid 38596280)
10. Levis M, Brown P, Smith BD, et al. Plasma inhibitory activity (PIA): a pharmacodynamic assay reveals insights into the basis for cytotoxic response to FLT3 inhibitors. Blood. 2006;108(10):3477-3483.
11. Pratz KW, Cortes J, Roboz GJ, et al. A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response. Blood. 2009;113:3938-3946.
12. Knapper S, Mills KI, Gilkes AF, Austin SJ, Walsh V, Burnett AK. The effects of lestaurtinib (CEP701) and PKC412 on primaryAMLblasts: the induction of cytotoxicity varies with dependence on FLT3 signaling in both FLT3-mutated and wild-type cases. Blood. 2006;108(10):3494-3503.
13. Levis M, Allebach J, Tse KF, et al. A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo. Blood. 2002;99(11):3885-3891. (Pubitemid 35332023)
14. Shiotsu Y, Kiyoi H, Ozeki K, et al. KW-2449, a novel multi-kinase inhibitor against FLT3, Abl, FGFR1 and Aurora, suppresses the growth of AML both in vitro and in vivo [abstract]. Blood. 2007;118:542a. Abstract 1832.
15. Zarrinkar PP, Gunawardane RN, Cramer MD, et al. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). Blood. 2009;114(14):2984-2992.
16. Auclair D, Miller D, Yatsula V, et al. Antitumor activity of sorafenib in FLT3-driven leukemic cells. Leukemia. 2007;21(3):439-445. (Pubitemid 46306554)
17. O'Farrell AM, Abrams TJ, Yuen HA, et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood. 2003;101(9):3597-3605.
18. Levis M, Tse KF, Smith BD, Garrett E, Small D. A FLT3 tyrosine kinase inhibitor is selectively cytotoxic to acute myeloid leukemia blasts harboring FLT3 internal tandem duplication mutations. Blood. 2001;98(3):885-887.
19. Murphy KM, Levis M, Hafez MJ, et al. Detection of FLT3 internal tandem duplication and D835 mutations by a multiplex polymerase chain reaction and capillary electrophoresis assay. J Mol Diagn. 2003;5(2):96-102. (Pubitemid 36553429)
20. Stirewalt DL, Willman CL, Radich JP. Quantitative, real-time polymerase chain reactions for FLT3 internal tandem duplications are highly sensitive and specific. Leuk Res. 2001;25(12):1085-1088.
21. Kelly LM, Yu JC, Boulton CL, et al. CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Cancer Cell. 2002;1(5):421-432.
22. Hayakawa F, Towatari M, Kiyoi H, et al. Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines. Oncogene. 2000;19(5):624-631. (Pubitemid 30102913)
23. Sato T, Knapper S, Burnett A, White P, Levis M. Increased plasma FLT3 ligand levels following chemotherapy may interfere with the clinical efficacy of FLT3 inhibitors [abstract]. Blood. 2009;114:937a. Abstract 937.
24. Armstrong SA, Kung AL, Mabon ME, et al. Inhibition of FLT3 in MLL: validation of a therapeutic target identified by gene expression based classification. Cancer Cell. 2003;3(2):173-183.
25. Marshall JL, Kindler H, Deeken J, et al. Phase I trial of orally administered CEP-701, a novel neurotrophin receptor-linked tyrosine kinase inhibitor. Invest New Drugs. 2005;23(1):31-37. (Pubitemid 39505949)
26. Propper DJ, McDonald AC, Man A, et al. Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C. J Clin Oncol. 2001;19(5):1485-1492. (Pubitemid 32202557)
27. Strumberg D, Richly H, Hilger RA, et al. Phase I clinical and pharmacokinetic study of the novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J Clin Oncol. 2005;23(5):965-972. (Pubitemid 46202316)
28. Faivre S, Delbaldo C, Vera K, et al. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol. 2006;24(1):25-35. (Pubitemid 46630490)
29. Breitenbuecher F, Markova B, Kasper S, et al. A novel molecular mechanism of primary resistance to FLT3-kinase inhibitors in AML. Blood. 2009;113(17):4063-4073.
30. Meggio F, Donella Deana A, Ruzzene M, et al. Different susceptibility of protein kinases to staurosporine inhibition: kinetic studies and molecular bases for the resistance of protein kinase CK2. Eur J Biochem. 1995;234(1):317-322.
31. Karaman MW, Herrgard S, Treiber DK, et al. A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol. 2008;26(1):127-132.
32. Shih LY, Huang CF, Wu JH, et al. Internal tandem duplication of FLT3 in relapsed acute myeloid leukemia: a comparative analysis of bone marrow samples from 108 adult patients at diagnosis and relapse. Blood. 2002;100(7):2387-2392.
33. Kottaridis PD, Gale RE, Langabeer SE, Frew ME, Bowen DT, Linch DC. Studies of FLT3 mutations in paired presentation and relapse samples from patients with acute myeloid leukemia: implications for the role of FLT3 mutations in leukemogenesis, minimal residual disease detection, and possible therapy with FLT3 inhibitors. Blood. 2002;100(7):2393-2398.
34. Nakano Y, Kiyoi H, Miyawaki S, et al. Molecular evolution of acute myeloid leukaemia in relapse: unstable N-ras and FLT3 genes compared with p53 gene. Br J Haematol. 1999;104(4):659-664. (Pubitemid 29143481)