130
Views
2
CrossRef citations to date
0
Altmetric
Hematological Malignancy: Current clinical practice

Molecular and chromosomal alterations: new therapies for relapsed acute myeloid leukemia

, , , , , , , & show all
Pages 1-12 | Published online: 18 Jul 2013

References

  • Palmero I, Pantoja C, Serrano M. p19ARF links the tumor suppressor p53 to RAS. Nature 1998; 395: 125–126.
  • Hayakawa F, Towatari M, Kiyoi H et al. Tandem-duplicated F1t3constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines. Oncogene 2000; 19: 624–631.
  • Delgado MD, Vague JP, Arozarena I et al. H-, K- and N-Rasinhibit myeloid leukemia cell proliferation by a p21WAF1-dependent mechanism. Oncogene 2000; 19: 783–790.
  • Kelly LM, Yu J, Boulton CL et al. CT53518, a novel selectiveFLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Cancer Cell 2002; 1: 421–432.
  • Burnett AK. The treatment of AML: current status and novelapproaches. Hematology 2005; 10: 50–53.
  • Aaronson SA. Growth factors and cancer. Science 1991; 254:1146–1153.
  • Falini B, Mecucci C, Tiacci E et al. Cytoplasmic nucleophosminin acute myelogenous leukemia with normal karyotype. N Engl J Med 2005; 352: 254–266
  • Agnes F, Shamoon B, Dina C, Rosnet O, Birnbaum D, GaBert F. Genomic structure of the downstream part of the human FLT3 gene: exon/intron structure conservation among genes encoding receptor tyrosine kinases (RTK) of subclass III. Gene 1994; 145: 283–288.
  • Broudy VC. Stem cell factor and hematopoiesis. Blood 1997; 90:1345–1364.
  • Rosnet O, Marchetto S, de Lapeyriere O, Birnbaum D. Murine F1t3, a gene encoding a novel tyrosine kinase receptor of the PDGFR/CSF1R family. Oncogene 1991; 6: 1641–1650.
  • Small D, Levenstein M, Kim E et al. STK-1, the human homologof Flk-2/Flt-3, is selectively expressed in CD34 + human bone marrow cells and is involved in the proliferation of early progenitor/stem cells. Proc Natl Acad Sci USA 1994; 91: 459–463.
  • Lyman SD. Biology of flt3 ligand and receptor. Int J Hematol 1995; 62: 63–73.
  • Lisovsky M, Estrov Z, Zhang X et al. F1t3 ligand stimulates proliferation and inhibits apoptosis of acute myeloid leukemia cells: regulation of Bc1-2 and Bax. Blood 1996; 88: 3987–3997.
  • Nakao M, Yokota S, Iwai T, et al Internal tandem duplication ofthe flt3 gene found in acute myeloid leukemia. Leukemia 1996; 10: 1911–1918.
  • Yamamoto Y, Kiyoi H, Nakano Y et al. Activating mutation ofD835 within the activation loop of FLT3 in human hematologic malignancies. Blood 2001; 97: 2434–2439.
  • Abu-Duhier FM, Goodeve AC, Wilson GA et al. Identification ofnovel FLT-3 Asp835 mutations in adult acute myeloid leukemia. Br J Haematol 2001; 113: 983–988.
  • Thiede C, Steudel C, Mohr B et al. Analysis of FLT3-activatingmutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood 2002; 99: 4326–4335.
  • Schnittger S, Schoch C, Dugas M et al. Analysis of FLT3 lengthmutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood 2002; 100: 59–66.
  • Kiyoi H, Towatari M, Yokota S et al. Internal tandem duplication of the FLT3 gene is a novel modality of elongation mutation which causes constitutive activation of the product. Leukemia 1998; 12: 1333–1337.
  • Kelly LM, Liu Q, Kutok JL, Williams IR, Boulton CL, GillilandDG. FLT3 internal tandem duplication mutations associated with human acute myeloid leukemias induce myeloproliferative disease in a murine bone marrow transplant model. Blood 2002; 99: 310–318.
  • Kelly LM, Kutok JL, Williams IR et al. PML/RARa and FLT3-ITD induce an APL-like disease in a mouse model. Proc Natl Acad Sci USA 2002; 99: 8283–8288.
  • Kiyoy H, Naoe T, Nakano Y et al. Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood 1999; 93: 3074–3080.
  • Frohling S, Schlenk RF, Breitruck J et al. Prognostic significanceof activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm. Blood 2002; 100: 4372–4380.
  • Kottaridis PD, Gale RE, Frew ME et al. The presence of a FLT3internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood 2001; 98: 1752–1759.
  • Smith ML, Arch R, Smith LL et al. Development of a human acute myeloid leukemia screening panel and consequent identifi-cation of novel gene mutation in FLT3 and CCND3. Br J Haematol 2005; 128: 318–323.
  • Stirewalt DL, Meshinchi S, Kussick Si et al. Novel FLT3 point mutations within exon 14 found in patients with acute myeloid leukemia. Br J Haematol 2004; 124: 481–484.
  • Care RS, Valk Pi, Goodeve AC et al. Incidence and prognosis ofc-KIT and FLT3 mutations in core binding factor (CBF) acute myeloid leukemias. Br J Haematol 2003; 121: 775–777.
  • Paschka P, Marcucci G, Ruppert AS et al. Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B Study. J Clin Oncol 2006; 24: 3904–3911.
  • Kohl TM, Schnittger S, Ellwart JW et al. KIT exon 8 mutationsassociated with core binding factor (CBF)-acute myeloid leuke-mia (AML) cause hyperactivation of the receptor in response to stem cell factor. Blood 2005; 105: 3319–3321.
  • Boguski MS, McCormick F. Proteins regulating Ras and its relatives. Nature 1993; 366: 643–654.
  • Bos JL. Ras oncogenes in human cancer: a review. Cancer Res 1989; 49: 4682–4689.
  • Zhang S, Mantel C, Broxmeyer HE. F1t3 signaling involves tyrosyl-phosphorylation of SHP-2 and SHIP and their association with Grb2 and Shc in Baf3/F1t3 cells. J Leukoc Biol 1999; 65: 372–380.
  • Lennartsson J, Blume-Jensen P, Hermanson M, Pontén E, Carlberg M, Rfinnstrand L. Phosphorylation of Shc by Src family kinases is necessary for stem cell factor receptor/c-kit mediated activation of the Ras/MAP kinase pathway and c-fos induction. Oncogene 1999; 18: 5546–5553.
  • Kang CD, Do IR, Kim KW et al. Role of Ras/ERK-dependentpathway in the erythroid differentiation of K562 cells. Exp Mol Med 1999; 31: 76–82.
  • Katz ME, McCormick F. Signal transduction from multiple Raseffectors. Curr Opin Genet Dev 1997; 7: 75–79.
  • Kauffmann-Zeh A, Rodriguez-Viciana P, Ulrich E et al. Suppression of c-Myc-induced apoptosis by Ras signalling through PI(3)K and PKB. Nature 1997; 385: 544–548.
  • Khosravi-Far R, White MA, Westwick JK, et al. Oncogenic Rasactivation of Raf/mitogen-activated protein kinase-independent pathways is sufficient to cause tumorigenic transformation. Mol Cell Biol 1996; 16: 3923–3933.
  • Kishida S, Koyama S, Matsubara K, Kishida M, Matsuura Y, Kikuchi A. Colocalization of Ras and Ral on the membrane is required for Ras-dependent Ral activation through Ral GDP dissociation stimulator. Oncogene 1997; 15: 2899–2907.
  • Clark GJ, Westwick JK, Der CJ. p120 GAP modulates Ras activation of Jun kinases and transformation. J Biol Chem 1997; 272: 1677–1681.
  • Moodie SA, Willumsen BM, Weber MJ, Wolfman A. Complexesof Ras. GTP with Raf-1 and mitogen-activated protein kinase kinase. Science 1993; 260: 1658–1661.
  • Lange-Carter CA, Pleiman CM, Gardner AM, Blumer KJ, Johnson GL. A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf. Science 1993; 260: 315–319.
  • Zhao Y, Bjorbaek C, Moller DE. Regulation and interaction of p90(rsk) isoforms with mitogen-activated protein kinases. J Biol Chem 1996; 271: 29773–29779.
  • Willard FS, Crouch MF. MEK, ERK, and p9ORSK are presenton mitotic tubulin in Swiss 3T3 cells: a role for the MAP kinase pathway in regulating mitotic exit. Cell Signal 2001; 13: 653–664.
  • Olson MF, Ashworth A, Hall A. An essential role for Rho, Rac,and Cdc42 GTPases in cell cycle progression through Gl. Science 1995; 269: 1270–1272.
  • Towatari M, Iida H, Tanimoto M, Iwata H, Hamaguchi M, SaitoH. Constitutive activation of mitogen-activated protein kinase pathway in acute leukemia cells. Leukemia 1997; 11: 479–484.
  • Iida M, Towatari M, Nakao A, et al. Lack of constitutive activation of MAP kinase pathway in human acute myeloid leukemia cells with N-Ras mutation. Leukemia 1999; 13: 585–589.
  • Morgan MA, Dolp O, Reuter CW. Cell-cycle-dependent activa-tion of mitogen-activated protein kinase kinase (MEK-1/2) in myeloid leukemia cell lines and induction of growth inhibition and apoptosis by inhibitors of RAS signaling. Blood 2001; 97: 1823–1834.
  • Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and pl 6INK4a. Cell 1997; 88: 593–602.
  • Gu H, Saito K, Klaman LD et al. Essential role for Gab2 in theallergic response. Nature 2001; 412: 186–190.
  • Serve H, Yee NS, Stella G, Sepp-Lorenzino L, Tan JC, Besmer P.Differential roles of P13-kinase and Kit tyrosine 821 in Kit receptor-mediated proliferation, survival and cell adhesion in mast cells. EMBO J 1995; 14: 473–483.
  • Martelli AM, Nyakern M, Tabellini G et al. Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia. Leukemia 2006; 20: 911–928.
  • Ihle JN. Signaling by the cytokine receptor superfamily in normaland transformed hematopoietic cells. Adv Cancer Res 1996; 68: 23–65.
  • Taniguchi T. Cytokine signaling through nonreceptor protein tyrosine kinases. Science 1995; 268: 251–255.
  • Rane SG, Reddy EP. JAKs, STATs and Src kinases in hematopoiesis. Oncogene 2002; 21: 3334–3358.
  • Birkenkamp KU, Geugien M, Lemmink HH, Kruijer W, Vellenga E. Regulation of constitutive STAT5 phosphorylation in acute myeloid leukemia blasts. Leukemia 2001; 15: 1923–1931.
  • Schuringa ii, Wierenga AT, Kruijer W et al. Constitutive Stat3,Tyr705, and 5er727 phosphorylation in acute myeloid leukemia cells caused by the autocrine secretion of interleukin-6. Blood 2000; 95: 3765–3770.
  • Ning ZQ, Li J, Arceci RJ. Signal transducer and activator of transcription 3 activation is required for Asp(816) mutant c-Kit-mediated cytokine-independent survival and proliferation in human leukemia cells. Blood 2001; 97: 3559–3567.
  • Lacronique V, Bureaux A, Valle VD et al. A TEL-JAK2 fusionprotein with constitutive kinase activity in human leukemia. Science 1997; 278: 1309–1312.
  • Larson RA, Williams SF, Le Beau MM et al. Acute myelomo-nocytic leukemia with abnormal eosinophils and inv(16) or t(16;16) has a favorable prognosis. Blood 1986; 68: 1242–1249.
  • Schoch C, Haase D, Haferlach T et al. Fifty-one patients with acute myeloid leukemia and translocation t(8;21)(q22;q22): an additional deletion in 9q is an adverse prognostic factor. Leukemia 1996; 10: 1288–1295.
  • Fenaux P, Chastang C, Chevret S et al. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood 1999; 94: 1192–1200.
  • Burnett AK, Grimwade D, Solomon E, Wheatley K, Goldstone AH. Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the Randomized MRC Trial. Blood 1999; 93: 4131–4143.
  • Wheatley K, Burnett AK, Goldstone AH et al. A simple, robust,validated and highly predictive index for the determination of risk-directed therapy in acute myeloid leukaemia derived from the MRC AML 10 trial. United Kingdom Medical Research Council's Adult and Childhood Leukaemia Working Parties. Br J Haematol 1999; 107: 69–79.
  • Rowe D, Cotterill Si, Ross FM et al. Cytogenetically cryptic AML1-ETO and CBF beta-MYH11 gene rearrangements: incidence in 412 cases of acute myeloid leukaemia. Br J Haematol 2000; 111: 1051–1056.
  • Byrd JC, Mrozek K, Dodge RK et al. Pretreatment cyotgenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 2002; 100: 4325–4336.
  • Friedman AD. Leukemogenesis by CBF Oncoproteins. Leukemia 1999; 13: 1932–1342.
  • Tobal K, Yin JA. Monitoring of minimal residual disease by quantitative reverse transcriptase-polymerase chain reaction for AML1-MTG8 transcripts in AML-M2 with t(8; 21). Blood 1996; 88: 3704–3709.
  • Wang J, Saunthararajah Y, Redner RL, Liu JM. Inhibitors of histone deacetylase relieve ETO-mediated repression and induce differentiation of AML1-ETO leukemia cells. Cancer Res 1999; 59: 2766–2769.
  • Giguere V, Ong ES, Segui P, Evans RM. Identification of a receptor for the morphogen retinoic acid. Nature 1987; 330: 624–629.
  • Rowley JD, Golomb HM, Dougherty C. 15/17 translocation, a consistent chromosomal change in acute promyelocytic leukae-mia. Lancet 1977; 1: 549–550.
  • Zelent A, Guidez F, Melnick A, Waxman S, Licht JD. Translocations of the RARalpha gene in acute promyelocytic leukemia. Oncogene 2001; 20: 7186–7203.
  • Zhou GB, Chen Si, Chen Z. Acute promyelocitic leukemia: a model of molecular target based therapy. Hematology 2005; 10: 270–280.
  • Kelly LM, Kutok JL, Williams IR et al. PML/RARalpha and FLT3-ITD induce an APL-like disease in a mouse model. Proc Natl Acad Sci USA 2002; 99: 8283–8288.
  • Rowley JD. Molecular genetics in acute leukemia. Leukemia 2000; 14: 513–517.
  • Dohner K, Tobis K, Ulrich R et al. Prognostic significance of partial tandem duplications of the MLL gene in adult patients 16-60 years old with acute myeloid leukemia and normal cytoge-netics: a study of the Acute Myeloid Leukemia Study Group Ulm. J Clin Oncol 2002; 20: 3254–3261.
  • Cuneo A, Ferrant A, Michaux JL et al. Philadelphia chromo-some-positive acute myeloid leukemia: cytoimmunologic and cytogenetic features. Haematologiea 1996; 81: 423–427.
  • Radich J, Gehly G, Lee A et al. Detection of bcr-abl transcriptsin Philadelphia chromosome-positive acute lymphoblastic leukemia after marrow transplantation. Blood 1997; 89: 2602–2609.
  • Carroll M, Ohno-Jones S, Tamura S et al. CGP 57148, a tyrosinekinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins. Blood 1997; 90: 4947–4952.
  • Druker BJ, Sawyers CL, Kantarjian H et al. Activity of a specificinhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 2001; 344: 1038–1042.
  • Heinrich MC, Griffith DJ, Druker BJ et al. Inhibition of c-kitreceptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood 2000; 96: 925–932.
  • Beghini A, Cairoli R, Morra E, Larizza L. In vivo differentiationof mast cells from acute myeloid leukemia blasts carrying a novel activating ligand-independent C-kit mutation. Blood Cells Mol Dis 1998; 24: 262–270.
  • Malagola M, Martinelli G, Rondoni M et al. Imatinib mesylate inthe treatment of c-kit-positive acute myeloid leukaemia: is this the real target? Blood 2005; 105: 904–905.
  • Smolich BD, Yuen HA, West KA et al. The antiangiogenic protein kinase inhibitors 5U5416 and 5U6668 inhibit the SCF receptor (c-kit) in a human myeloid leukemia cell line and in acute myeloid leukemia blasts. Blood 2001; 97: 1413–1421.
  • Mesters RM, Padro T, Bieker R et al. Stable remission after administration of the receptor tyrosine kinase inhibitor 5U5416 in a patient with refractory acute myeloid leukemia. Blood 2001; 98: 241–243.
  • Kuenen BC, Rosen L, Smit EF et al. Dose-finding and pharmacokinetic study of cisplatin, gemcitabine, and SU5416 in patients with solid tumors. J Clin Oncol 2002; 20: 1657–1667.
  • Growney JD, Clark ii, Adelsperger J et al. Activation mutationsof human c-KIT resistant to imatinib are sensitive to the tyrosine kinase inhibitor PKC412. Blood 2005; 106: 721–724
  • DeAngelo DJ, Stone RM, Heaney ML et al. Phase 1 clinical results with tandutinib (MLN518), a novel FLT3 antagonist, in patients with acute myelogenous leukemia or high-risk myelo-dysplastic syndrome: safety, pharmacokinetics, and pharmacody-namics. Blood 2006; 108: 3674–3681.
  • Smith BD, Levis M, Beran Met al. Single-agent CEP-701, a novelFLT3 inhibitor, shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemia. Blood 2004; 103: 3669–3676.
  • Giles FJ, Cooper MA, Silverman L et al. Phase II study of 5U5416-a small-molecule, vascular endothelial growth factor tyrosine-kinase receptor inhibitor-in patients with refractory myeloproliferative diseases. Cancer 2003; 97: 1920–1928.
  • Giles FJ, Stopeck AT, Silverman LR et al. 5U5416, a small molecule tyrosine kinase receptor inhibitor, has biologic activity in patients with refractory acute myeloid leukemia or myelodys-plastic syndromes. Blood 2003; 102: 795–801.
  • O'Farrell AM, Yuen HA, Smolich B et al. Effects of 5U5416, asmall molecule tyrosine kinase receptor inhibitor, on FLT3 expression and phosphorylation in patients with refractory acute myeloid leukemia. Leuk Res 2004; 28: 679–689.
  • Fiedler W, Mesters R, Tinnefeld H et al. A phase 2 clinical study of 5U5416 in patients with refractory acute myeloid leukemia. Blood 2003; 102: 2763–2767.
  • O'Farrell AM, Foran JM, Fiedler W et al. An innovative phase Iclinical study demonstrates inhibition of FLT3 phosphorylation by SU11248 in acute myeloid leukemia patients. Clin Cancer Res 2003; 9: 5465–5476.
  • Fiedler W, Serve H, Dohner H et al. A phase 1 study of SU11248in the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for the disease. Blood 2005; 105: 986–993.
  • Stone RM, DeAngelo DJ, Klimek V et al. Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412. Blood 2005; 105: 54–60.
  • Levis M, Pharm R, Smith BD, Small D. In vitro studies of a FLT3inhibitor combined with chemotherapy: sequence of administra-tion is important to achieve synergistic cytotoxic effects. Blood 2004; 104: 1145–1150
  • Ikeda A, Shankar DB, Watanabe M, Tamanoi F, Moore TB, Sakamoto KM. Molecular targets and the treatment of myeloid leukemia. Mol Genet Metab 2006; 88: 216–224.
  • Lerner EC, Qian Y, Blaskovich MA et al. Ras CAAX peptidomimetic FTI-277 selectively blocks oncogenic Ras signal-ing by inducing cytoplasmic accumulation of inactive Ras-Raf complexes. J Biol Chem 1995; 270: 26802–26806.
  • Cox AD, Garcia AM, Westwick JK et al. The CAAX peptidomimetic compound B581 specifically blocks farnesylated, but not geranylgeranylated or myristylated, oncogenic ras signalling and transformation. J Biol Chem 1994; 269: 19203–19206.
  • Miguel K, Pradines A, Sun J et al. GGTI-298 induces GO-G1 block and apoptosis whereas FTI-277 causes G2-M enrichment in A549 cells. Cancer Res 1997; 57: 1846–1850.
  • Sepp-Lorenzino L, Rosen N. A farnesyl-protein transferase inhibitor induces p21 expression and G1 block in p53 wild type tumour cells. J Biol Chem 1998; 273: 20243–20251.
  • Oliff A. Farnesyltransferase inhibitors: targeting the molecular basis of cancer. Biochim Biophys Acta 1999; 1423: C19–C30.
  • Lebowitz PF, Prendergast GC. Non-Ras targets of farnesyltrans-ferase inhibitors: focus on Rho. Oncogene 1998; 17: 1439–1445.
  • Liu A, Du W, Liu JP, Jessell TM, Prendergast GC. RhoB alteration is necessary for apoptotic and antineoplastic responses to farnesyltransferase inhibitors. Mol Cell Biol 2000; 20: 6105–6113.
  • Adjei AA, Erlichman C, Davis JN et al. A Phase I trial of the farnesyl transferase inhibitor 5CH66336: evidence for biological and clinical activity. Cancer Res 2000; 60: 1871–1877.
  • Hoover RR, Mahon FX, Melo JV, Daley GQ. Overcoming 5TI571 resistance with the farnesyl transferase inhibitor 5CH66336. Blood 2002; 100: 1068–1071.
  • Peters DG, Hoover RR, Gerlach MJ et al. Activity of the farnesylprotein transferase inhibitor 5CH66336 against BCR/ABL-induced murine leukemia and primary cells from patients with chronic myeloid leukemia. Blood 2001; 97: 1404–1412.
  • Karp JE, Lancet JE, Kaufmann SH et al. Clinical and biologic activity of the farnesyltransferase inhibitor R115777 in adults with refractory and relapsed acute leukemias: a phase 1 clinical laboratory correlative trial. Blood 2001; 97: 3361–3369.
  • Crul M, de Clerk GJ, Swart M et al. Phase I clinical and pharmacologic study of chronic oral administration of the farnesyl protein transferase inhibitor R115777 in advanced cancer. J Clin Oncol 2002; 20: 2726–2735.
  • Morgan MA, Dolp O, Reuter CW. Cell-cycle-dependent activa-tion of mitogen-activated protein kinase kinase (MEK-1/2) in myeloid leukemia cell lines and induction of growth inhibition and apoptosis by inhibitors of RAS signaling. Blood 2001; 97: 1823–1834.
  • Frank DA. STAT signaling in the pathogenesis and treatment of cancer. Mol Med 1999; 5: 432–456.
  • Marra F, Choudhury GG, Abboud HE. Interferon-c-mediated activation of STAT la regulates growth factor-induced mitogen-esis. J Clin Invest 1996; 98: 1218–1230.
  • Xu F, Taki T, Yang HW et al. Tandem duplication of the FLT3 gene is found in acute lymphoblastic leukaemia as well as acute myeloid leukaemia but not in myelodysplastic syndrome or juvenile chronic myelogenous leukaemia in children. Br J Haematol 1999; 105: 155–162.
  • Stirewalt DL, Kopecky KJ, Meshinchi S et al. FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. Blood 2001; 97: 3589–3595.
  • Meshinchi S, Woods WG, Stirewalt DL et al. Prevalence and prognostic significance of FLT3 internal tandem dupli-cation in pediatric acute myeloid leukemia. Blood 2001; 97: 89–94.
  • Ridge SA, Worwood M, Oscier D et al. FMS mutations in myelodysplastic, leukemic, and normal subjects. Proc Natl Acad Sci USA 1990; 87: 1377–1380.
  • Tobal K, Pagliuca A, Bhatt B, Bailey N, Layton DM, Mufti GJ. Mutation of the human FMS gene (M-CSF receptor) in myelodysplastic syndromes and acute myeloid leukemia. Leukemia 1990; 4: 486–489.
  • Padua RA, Guinn BA, Al-Sabah AT et al. RAS, FMS and p53 mutations and poor clinical outcome in myelodysplasias: a 10-year follow-up. Leukemia 1998; 12: 887–892.
  • Gari M, Goodeve A, Wilson G et al. c-kit proto-oncogene exon 8 in-frame deletion plus insertion mutations in acute myeloid leukaemia. Br J Haematol 1999; 105: 894–900.
  • Sperr WR, Walchshofer S, Horny HP et al. Systemic mastocytosis associated with acute myeloid leukaemia: report of two cases and detection of the c-kit mutation Asp-816 to Val. Br J Haematol 1998; 103: 740–749.
  • Farr CJ, Saiki RK, Erlich HA, McCormick F, Marshall CJ. Analysis of RAS gene mutations in acute myeloid leukemia by polymerase chain reaction and oligonucleotide probes. Proc Natl Acad Sci USA 1988; 85: 1629–1633.
  • Bartram CR, Ludwig WD, Hiddemann W et al. Acute myeloid leukemia: analysis of ras gene mutations and clonality defined by polymorphic X-linked loci. Leukemia 1989; 3: 247–256.
  • Radich JP, Kopecky KJ, Willman CL et al. N-ras mutations in adult de novo acute myelogenous leukemia: prevalence and clinical significance. Blood 1990; 76: 801–807.
  • Bos JL, Verlaan-de Vries M, van der Eb Ai et al. Mutations in N-ras predominate in acute myeloid leukemia. Blood 1987; 69: 1237–1241.
  • Neubauer A, Dodge RK, George SL et al. Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia. Blood 1994; 83: 1603–1611.
  • Morgan MA and Reuter CV. Molecularly targeted therapies in myelodysplastic syndromes and acute myeloid leukemias. Ann Hematol 2006; 85: 139–163.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.