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Review Article

Advances in the biology and therapy of chronic myeloid leukemia: proceedings from the 6th Post-ASH International Chronic Myeloid Leukemia and Myeloproliferative Neoplasms Workshop

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Pages 1151-1158 | Received 27 Aug 2012, Accepted 27 Oct 2012, Published online: 10 Dec 2012

References

  • Duy C, Hurtz C, Shojaee S, et al. BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR-ABL1 kinase inhibition. Nature 2011;473:384–388.
  • Hurtz C, Hatzi K, Cerchietti L, et al. BCL6-mediated repression of p53 is critical for leukemia stem cell survival in chronic myeloid leukemia. J Exp Med 2011;208:2163–2174.
  • Zhang H, Li H, Xi HS, et al. HIF1alpha is required for survival maintenance of chronic myeloid leukemia stem cells. Blood 2012; 119:2595–2607.
  • Hantschel O, Warsch W, Eckelhart E, et al. BCR-ABL uncouples canonical JAK2-STAT5 signaling in chronic myeloid leukemia. Nat Chem Biol 2012;8:285–293.
  • Walz C, Ahmed W, Lazarides K, et al. Essential role for Stat5a/b in myeloproliferative neoplasms induced by BCR-ABL1 and Jak2V617F in mice. Blood 2012;119:3550–3560.
  • Yuan H, Wang Z, Li L, et al. Activation of stress response gene SIRT1 by BCR-ABL promotes leukemogenesis. Blood 2012;119:1904–1914.
  • Li L, Wang L, Li L, et al. Activation of p53 by SIRT1 inhibition enhances elimination of CML leukemia stem cells in combination with imatinib. Cancer Cell 2012;21:266–281.
  • Goff D, Smith KM, Shih A, et al. BCL2 splice isoform switching promotes leukemia stem cell survival and sensitivity to a novel pan BCL2 inhibitor. Blood 2011;118: Abstract 2735.
  • Shih A, Schairer A, Barrett CL, et al. Cycling toward leukemia stem cell elimination wtih a selective sonic hedgehog antagonist. Blood 2011;118: Abstract 3776.
  • Neviani P, Santhanam R, Oaks JJ, et al. FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemia. J Clin Invest 2007;117:2408–2421.
  • Oaks JJ, Mukhopadhyay A, Santhanam R, et al. FTY720 restores PP2A tumor suppressor activity in polycythemia vera CD34 + progenitors through inhibition of Jak2 V617F- and PI-3Kγ-dependent SET serine phosphorylation and enhancement of NOS-dependent PP2A tyrosine nitration. Blood 2011;118: Abstract 2494.
  • Agarwal A, MacKenzie R, Oddo J, et al. A novel SET antagonist (OP449) is cytotoxic to CML cells, including the highly-resistant BCR-ABL T315I mutant, and demonstrates enhanced efficacy in combination with ABL tyrosine kinase inhibitors. Blood 2011;118: bstract 3757.
  • Nieborowska-Skorska M, Kopinski PK, Ray R, et al. Rac2-MRC-cIII-generated ROS cause genomic instability in chronic myeloid leukemia stem cells and primitive progenitors. Blood 2012;119:4253–4263.
  • Bolton E, Schemionek M, Klein H-U, et al. Genomic instability originates from leukemia stem cells in a mouse model of CML-CP. Blood 2011;118: Abstract 445.
  • Slupianek A, Dasgupta Y, Ren SY, et al. Targeting RAD51 phosphotyrosine-315 to prevent unfaithful recombination repair in BCR-ABL1 leukemia. Blood 2011;118:1062–1068.
  • Cramer K, Bolton E, Nieborowska-Skorska M, et al. Targeting DNA repair gene, RAD52, induces exhaustion of the proliferating CML-CP leukemia stem cells carrying oxidative DNA damage. Blood 2011; 118: Abstract 447.
  • Raaijmakers MH, Mukherjee S, Guo S, et al. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature 2010;464:852–857.
  • Adams GB, Martin RP, Alley IR, et al. Therapeutic targeting of a stem cell niche. Nat Biotechnol 2007;25:238–243.
  • Krause DS, Fulzele K, Catic A, et al. Parathyroid hormone-induced modulation of the bone marrow microenvironment reduces leukemic stem cells in murine chronic myelogenous-leukemia-like disease via a TGFbeta-dependent pathway. Blood 2011;118: Abstract 1670.
  • Yamamoto-Sugitani M, Kuroda J, Ashihara E, et al. Galectin-3 (Gal-3) induced by leukemia microenvironment promotes drug resistance and bone marrow lodgment in chronic myelogenous leukemia. Proc Natl Acad Sci USA 2011;108:17468–17473.
  • Herrmann HD, Sadovnik I, Cerny-Reiterer S, et al. The leukemic stem cell (LSC) in Ph+ CML is a CD34+/CD38−/Lin− cell that co-expresses dipeptidylpeptidase IV (CD26) and disrupts LSC-niche interactions by degrading the CXCR4 ligand SDF-1α. Blood 2011; 118: Abstract 961.
  • Soverini S, De Benedittis C, Gnani A, et al. Ultra-deep amplicon sequencing using Roche 454 technology allows high sensitivity Bcr-Abl kinase domain mutation screening and anticipates emerging mutations leading to resistance to tyrosine kinase inhibitors in Philadelphia-positive leukemia patients. Blood 2011;118: Abstract 3775.
  • Ng KP, Hillmer AM, Chuah CT, et al. A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer. Nat Med 2012;18:521–528.
  • Saglio G, Kim DW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010;362: 2251–2259.
  • Kantarjian HM, Hochhaus A, Saglio G, et al. Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. Lancet Oncol 2011;12:841–851.
  • Saglio G, LeCoutre PD, Pasquini R, et al. Nilotinib versus imatinib in patients with newly diagnosed philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 36-month follow-up. Blood 2011;118: Abstract 452.
  • Larson RA, Hochhaus A, Hughes TP, et al. Nilotinib vs imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 3-year follow-up. Leukemia 2012;26:2197–2203.
  • Quintas-Cardama A, Kantarjian H, Luthra R, et al. Efficacy of frontline nilotinib therapy in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in early chronic phase. Blood 2011;118: Abstract 454.
  • Gugliotta G, Castagnetti F, Breccia M, et al. Early CP CML, nilotinib 400 mg twice daily frontline: beyond 3 years, results remain excellent and stable (a GIMEMA CML Working Party Trial). Blood 2011;118: Abstract 2756.
  • Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2010;362:2260–2270.
  • Kantarjian HM, Shah NP, Cortes JE, et al. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood 2012; 119:1123–1129.
  • Cortes JE, Kim DW, Kantarjian HM, et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial. J Clin Oncol 2012;30:3486–3492.
  • Cortes JE, Maru A, De Souza C, et al. Bosutinib versus imatinib in newly diagnosed chronic phase chronic myeloid leukemia – BELA trial: 24-month follow-up. Blood 2011;118: Abstract 455.
  • Mahon FX, Rea D, Guilhot J, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol 2010;11: 1029–1035.
  • Mahon FX, Rea D, Guilhot J, et al. Discontinuation of imatinib in patients with chronic myeloid leukemia who have maintained complete molecular response: update results of the STIM study. Blood 2011;118: Abstract 603.
  • Rea D, Rousselot P, Nicolini F, et al. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia (CML) patients (pts) with stable undetectable Bcr-Abl transcripts: results from the French CML group (FILMC). Blood 2011;118: Abstract 604.
  • Kumari A, Brendel C, Hochhaus A, et al. Low BCR-ABL expression levels in hematopoietic precursor cells enable persistence of chronic myeloid leukemia under imatinib. Blood 2012;119:530–539.
  • Chomel JC, Sorel N, Guilhot J, et al. BCR-ABL expression in leukemic progenitors and primitive stem cells of patients with chronic myeloid leukemia. Blood 2012;119:2964–2965.
  • Yeung D, Osborn M, White D, et al. Upfront imatinib therapy in CML patients with rapid switching to nilotinib for failure to achieve molecular targets or intolerance achieves high overall rates of molecular response and a low risk of progression - an update of the TIDEL-II trial. Blood 2011;118: Abstract 451.
  • Hughes TP, Lipton JH, Leber B, et al. Complete molecular response rate with nilotinib in patients with chronic myeloid leukemia in chronic phase without CMR after ≥ 2 years on imatinib: preliminary results from the randomized ENESTcmr trial of nilotinib 400 mg twice daily vs imatinib. Blood 2011;118: Abstract 606.
  • O’Hare T, Shakespeare WC, Zhu X, et al. AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell 2009;16:401–412.
  • Cortes JE, Kim DW, Pinilla-Ibarz J, et al. Initial findings from the PACE trial: a pivotal phase 2 study of ponatinib in patients with CML and Ph+ ALL resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation. Blood 2011;118: Abstract 109.
  • Chan WW, Wise SC, Kaufman MD, et al. Conformational control inhibition of the BCR-ABL1 tyrosine kinase, including the gatekeeper T315I mutant, by the switch-control inhibitor DCC-2036. Cancer Cell 2011;19:556–568.
  • Cortes JE, Talpaz M, Kantarjian H, et al. A phase 1 study of DCC-2036, a novel oral inhibitor of BCR-ABL kinase, in patients with Philadelphia chromosome positive (Ph+) leukemias including patients with T315I mutation. Blood 2011;118: Abstract 601.
  • Hughes T, Branford S. Molecular monitoring of BCR-ABL as a guide to clinical management in chronic myeloid leukemia. Blood Rev 2006;20:29–41.
  • Hughes TP, Kaeda J, Branford S, et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med 2003;349: 1423–1432.
  • Druker BJ, Guilhot F, O’Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006;355:2408–2417.
  • Branford S, Seymour JF, Grigg A, et al. BCR-ABL messenger RNA levels continue to decline in patients with chronic phase chronic myeloid leukemia treated with imatinib for more than 5 years and approximately half of all first-line treated patients have stable undetectable BCR-ABL using strict sensitivity criteria. Clin Cancer Res 2007;13:7080–7085.
  • Jabbour E, Kantarjian H, O’Brien S, et al. The achievement of an early complete cytogenetic response is a major determinant for outcome in patients with early chronic phase chronic myeloid leukemia treated with tyrosine kinase inhibitors. Blood 2011;118:4541–4546.
  • Milojkovic D, Gerrard G, Paliompeis C, et al. The natural history of RTQ-PCR levels after the achievement of complete molecular remission (CMR): implications for “stopping” studies. Blood 2011;118: Abstract 605.
  • Latagliata R, Breccia M, Carmosino I, et al. Complete cytogenetic response after 3 months is a very early indicator of good response to imatinib as front-line treatment in chronic myelogenous leukemia. Blood 2011;118: Abstract 3783.
  • Marin D, Ibrahim AR, Lucas C, et al. Assessment of BCR-ABL1 transcript levels at 3 months is the only requirement for predicting outcome for patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. J Clin Oncol 2012;30:232–238.
  • Hanfstein B, Muller MC, Hehlmann R, et al. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia 2012;26:2096–2102.
  • Nicolini F, Hayette S, Labussiere H, et al. The month three major molecular response in chronic phase chronic myeloid leukemia on imatinib 400, nilotinib and dasatinib is a major prognostic factor for failure-free and progression-free survival. Blood 2011;118: Abstract 1684.
  • White DL, Saunders VA, Frede A, et al. The strategy of early nilotinib switch based on failure to achieve optimal molecular targets on imatinib may not overcome the negative impact of a low OCT-1 activity in de-novo CP-CML patients. Blood 2011;118: Abstract 1690.
  • Hochhaus A, Saglio G, Chuah C, et al. Dasatinib and imatinib-induced reductions in BCR-ABL transcript levels below 10% at 3 months are associated with improved responses in patients with newly diagnosed chronic myeloid leukemia in chronic phase: analysis of molecular response kinetics in the DASISION trial. Blood 2011; 118: Abstract 2767.
  • Marin D, Hedgley C, Clark RE, et al. Predictive value of early molecular response in patients with chronic myeloid leukemia treated with first-line dasatinib. Blood 2012;120:291–294.
  • Skorski T. BCR/ABL, DNA damage and DNA repair: implications for new treatment concepts. Leuk Lymphoma 2008;49:610–614.
  • Radich JP, Dai H, Mao M, et al. Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc Natl Acad Sci USA 2006;103:2794–2799.
  • Lange T, Ernst T, Pfirrmann M, et al. Absolute quantification of mutant T315I BCR-ABL transcripts at 6 months identifies imatinib resistant CML patients with a low probability to achieve MMR after 12 months on second line tyrosine kinase therapy. Blood 2011;118: Abstract 1679.
  • Parker WT, Ho M, Scott HS, et al. Multiple low level mutations identifies imatinib resistant CML patients at risk of poor response to second-line inhibitor therapy, irrespective of the resistance profile of the mutations. Blood 2011;118: Abstract 111.
  • Okimoto RA, Van Etten RA. Navigating the road toward optimal initial therapy for chronic myeloid leukemia. Curr Opin Hematol 2011;18:89–97.

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