Mutational landscape of chronic myeloid leukemia: more than a single oncogene leukemia

References

• Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2020 update on diagnosis, therapy and monitoring. Am J Hematol. 2020;95(6):691–709.
   PubMed Web of Science ®Google Scholar
• Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34(4):966–984.
   PubMed Web of Science ®Google Scholar
• Cilloni D, Saglio G. Molecular pathways: BCR-ABL. Clin Cancer Res. 2012;18(4):930–937.
   PubMed Web of Science ®Google Scholar
• Mughal TI, Goldman JM. Targeting cancers with tyrosine kinase inhibitors: lessons learned from chronic myeloid leukaemia. Clin Med (Lond). 2006;6(6):526–528.
   PubMed Web of Science ®Google Scholar
• Bower H, Björkholm M, Dickman PW, et al. Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population. J Clin Oncol. 2016;34(24):2851–2857.
   PubMed Web of Science ®Google Scholar
• Russo D, Garcia-Gutierrez JV, Soverini S, et al. Chronic myeloid leukemia prognosis and therapy: criticisms and perspectives. J Clin Med. 2020;9(6):1709.
   PubMed Web of Science ®Google Scholar
• Mahon F-X. Treatment-free remission in CML: who, how, and why? Hematology Am Soc Hematol Educ Program. 2017;2017(1):102–109.
   PubMedGoogle Scholar
• Molica M, Naqvi K, Cortes JE, et al. Treatment-free remission in chronic myeloid leukemia. Clin Adv Hematol Oncol. 2019;17(12):686–696.
   PubMed Web of Science ®Google Scholar
• Baccarani M, Abruzzese E, Accurso V, et al. Managing chronic myeloid leukemia for treatment-free remission: a proposal from the GIMEMA CML WP. Blood Adv. 2019;3(24):4280–4290.
   PubMed Web of Science ®Google Scholar
• Melo JV, Barnes DJ. Chronic myeloid leukaemia as a model of disease evolution in human cancer. Nat Rev Cancer. 2007;7(6):441–453.
   PubMed Web of Science ®Google Scholar
• Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science. 1990;247(4944):824–830.
   PubMed Web of Science ®Google Scholar
• Zhang X, Ren R. BCR-ABL efficiently induces a myeloproliferative disease and production of excess interleukin-3 and granulocyte-macrophage colony-stimulating factor in mice: a novel model for chronic myelogenous leukemia. Blood. 1998;92(10):3829–3840.
   PubMed Web of Science ®Google Scholar
• Hochhaus A, La Rosée P. Imatinib therapy in chronic myelogenous leukemia: strategies to avoid and overcome resistance. Leukemia. 2004;18(8):1321–1331.
   PubMed Web of Science ®Google Scholar
• Soverini S, de Benedittis C, Mancini M, et al. Mutations in the BCR-ABL1 kinase domain and elsewhere in chronic myeloid leukemia. Clin Lymphoma Myeloma Leuk. 2015;15:S120–S128.
   PubMedGoogle Scholar
• Braun TP, Eide CA, Druker BJ. Response and resistance to BCR-ABL1-targeted therapies. Cancer Cell. 2020;37(4):530–542.
   PubMed Web of Science ®Google Scholar
• Bavaro L, Martelli M, Cavo M, et al. Mechanisms of disease progression and resistance to tyrosine kinase inhibitor therapy in chronic myeloid leukemia: an update. IJMS. 2019;20(24):6141.
   Google Scholar
• Patel AB, O'Hare T, Deininger MW. Mechanisms of resistance to ABL kinase inhibition in chronic myeloid leukemia and the development of next generation ABL kinase inhibitors. Hematol Oncol Clin North Am. 2017;31(4):589–612.
   PubMed Web of Science ®Google Scholar
• Hehlmann R, Lauseker M, Jung-Munkwitz S, et al. Tolerability-adapted imatinib 800 mg/d versus 400 mg/d versus 400 mg/d plus interferon-α in newly diagnosed chronic myeloid leukemia. J Clin Oncol. 2011;29(12):1634–1642.
   PubMed Web of Science ®Google Scholar
• Jain P, Kantarjian HM, Ghorab A, et al. Prognostic factors and survival outcomes in patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era: cohort study of 477 patients. Cancer. 2017;123(22):4391–4402.
   PubMed Web of Science ®Google Scholar
• Campiotti L, Suter MB, Guasti L, et al. Imatinib discontinuation in chronic myeloid leukaemia patients with undetectable BCR-ABL transcript level: a systematic review and a meta-analysis. Eur J Cancer. 2017;77:48–56.
   PubMed Web of Science ®Google Scholar
• Chomel JC, Bonnet ML, Sorel N, et al. Leukemic stem cell persistence in chronic myeloid leukemia patients in deep molecular response induced by tyrosine kinase inhibitors and the impact of therapy discontinuation. Oncotarget. 2016;7(23):35293–35301.
   PubMed Web of Science ®Google Scholar
• Hamilton A, Helgason GV, Schemionek M, et al. Chronic myeloid leukemia stem cells are not dependent on BCR-ABL kinase activity for their survival. Blood. 2012;119(6):1501–1510.
   PubMed Web of Science ®Google Scholar
• Graham SM, Jørgensen HG, Allan E, et al. Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood. 2002;99(1):319–325.
   PubMed Web of Science ®Google Scholar
• Houshmand M, Simonetti G, Circosta P, et al. Chronic myeloid leukemia stem cells. Leukemia. 2019;33(7):1543–1556.
   PubMed Web of Science ®Google Scholar
• Muselli F, Peyron J-F, Mary D. Druggable biochemical pathways and potential therapeutic alternatives to target leukemic stem cells and eliminate the residual disease in chronic myeloid leukemia. IJMS. 2019;20(22):5616.
   Google Scholar
• Boquett JA, Alves JRP, de Oliveira CEC. Analysis of BCR/ABL transcripts in healthy individuals. Genet Mol Res. 2013;12(4):4967–4971.
   PubMed Web of Science ®Google Scholar
• Fialkow PJ, Martin PJ, Najfeld V, et al. Evidence for a multistep pathogenesis of chronic myelogenous leukemia. Blood. 1981;58(1):158–163.
   PubMed Web of Science ®Google Scholar
• Burke B, Carroll M. BCR-ABL: a multi-faceted promoter of DNA mutation in chronic myelogeneous leukemia. Leukemia. 2010;24(6):1105–1112.
   PubMed Web of Science ®Google Scholar
• Soverini S, Gnani A, Colarossi S, et al. Philadelphia-positive patients who already harbor imatinib-resistant BCR-ABL kinase domain mutations have a higher likelihood of developing additional mutations associated with resistance to second- or third-line tyrosine kinase inhibitors. Blood. 2009;114(10):2168–2171.
   PubMed Web of Science ®Google Scholar
• Koptyra M, Cramer K, Slupianek A, et al. BCR/ABL promotes accumulation of chromosomal aberrations induced by oxidative and genotoxic stress. Leukemia. 2008;22(10):1969–1972.
   PubMed Web of Science ®Google Scholar
• Koptyra M, Falinski R, Nowicki MO, et al. BCR/ABL kinase induces self-mutagenesis via reactive oxygen species to encode imatinib resistance. Blood. 2006;108(1):319–327.
   PubMed Web of Science ®Google Scholar
• Slupianek A, Falinski R, Znojek P, et al. BCR-ABL1 kinase inhibits uracil DNA glycosylase UNG2 to enhance oxidative DNA damage and stimulate genomic instability. Leukemia. 2013;27(3):629–634.
   PubMed Web of Science ®Google Scholar
• Hehlmann R, Saußele S, Voskanyan A, et al. Management of CML-blast crisis. Best Pract Res Clin Haematol. 2016;29(3):295–307.
   PubMed Web of Science ®Google Scholar
• Jabbour EJ, Hughes TP, Cortés JE, et al. Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia. Leuk Lymphoma. 2014;55(7):1451–1462.
   PubMed Web of Science ®Google Scholar
• Xie M, Lu C, Wang J, et al. Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med. 2014;20(12):1472–1478.
   PubMed Web of Science ®Google Scholar
• Walter MJ. Antecedent CHIP in CML? Blood. 2017;129(1):3–4.
   PubMed Web of Science ®Google Scholar
• Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424–447.
   PubMed Web of Science ®Google Scholar
• Corm S, Biggio V, Roche-Lestienne C, et al. Coexistence of AML1/RUNX1 and BCR-ABL point mutations in an imatinib-resistant form of CML. Leukemia. 2005;19(11):1991–1992.
   PubMed Web of Science ®Google Scholar
• Roche-Lestienne C, Deluche L, Corm S, et al. RUNX1 DNA-binding mutations and RUNX1-PRDM16 cryptic fusions in BCR-ABL + leukemias are frequently associated with secondary trisomy 21 and may contribute to clonal evolution and imatinib resistance. Blood. 2008;111(7):3735–3741.
   PubMed Web of Science ®Google Scholar
• Roche-Lestienne C, Marceau A, Labis E, et al. Mutation analysis of TET2, IDH1, IDH2 and ASXL1 in chronic myeloid leukemia. Leukemia. 2011;25(10):1661–1664.
   PubMed Web of Science ®Google Scholar
• Menezes J, Salgado RN, Acquadro F, et al. ASXL1, TP53 and IKZF3 mutations are present in the chronic phase and blast crisis of chronic myeloid leukemia. Blood Cancer J. 2013;3:e157.
   PubMed Web of Science ®Google Scholar
• Valikhani A, Poopak B, Ferdowsi S, et al. ASXL1 and JAK2V617F gene mutation screening in Iranian patients with chronic myeloid leukemia. Asia Pac J Clin Oncol. 2017;13(2):e41–e47.
   PubMed Web of Science ®Google Scholar
• Soverini S, Score J, Iacobucci I, et al. IDH2 somatic mutations in chronic myeloid leukemia patients in blast crisis. Leukemia. 2011;25(1):178–181.
   PubMed Web of Science ®Google Scholar
• Schmidt M, Rinke J, Schäfer V, et al. Molecular-defined clonal evolution in patients with chronic myeloid leukemia independent of the BCR-ABL status. Leukemia. 2014;28(12):2292–2299.
   PubMed Web of Science ®Google Scholar
• Kim T, Tyndel MS, Kim HJ, et al. Spectrum of somatic mutation dynamics in chronic myeloid leukemia following tyrosine kinase inhibitor therapy. Blood. 2017;129(1):38–47.
   PubMed Web of Science ®Google Scholar
• Nteliopoulos G, Bazeos A, Claudiani S, et al. Somatic variants in epigenetic modifiers can predict failure of response to imatinib but not to second-generation tyrosine kinase inhibitors. Haematologica. 2019;104(12):2400–2409.
   PubMed Web of Science ®Google Scholar
• Ernst T, Busch M, Rinke J, et al. Frequent ASXL1 mutations in children and young adults with chronic myeloid leukemia. Leukemia. 2018;32(9):2046–2049.
   PubMed Web of Science ®Google Scholar
• Adnan Awad S, Kankainen M, Ojala T, et al. Mutation accumulation in cancer genes relates to nonoptimal outcome in chronic myeloid leukemia. Blood Adv. 2020;4(3):546–559.
   PubMed Web of Science ®Google Scholar
• Togasaki E, Takeda J, Yoshida K, et al. Frequent somatic mutations in epigenetic regulators in newly diagnosed chronic myeloid leukemia. Blood Cancer J. 2017;7(4):e559.
   PubMedGoogle Scholar
• Mitani K, Nagata Y, Sasaki K, et al. Somatic mosaicism in chronic myeloid leukemia in remission. Blood. 2016;128(24):2863–2866.
   PubMed Web of Science ®Google Scholar
• Mologni L, Piazza R, Khandelwal P, et al. Somatic mutations identified at diagnosis by exome sequencing can predict response to imatinib in chronic phase chronic myeloid leukemia (CML) patients. Am J Hematol. 2017;92(10):E623–E625.
   PubMed Web of Science ®Google Scholar
• Branford S, Wang P, Yeung DT, et al. Integrative genomic analysis reveals cancer-associated mutations at diagnosis of CML in patients with high-risk disease. Blood. 2018;132(9):948–961.
   PubMed Web of Science ®Google Scholar
• Ko TK, Javed A, Lee KL, et al. An integrative model of pathway convergence in genetically heterogeneous blast crisis chronic myeloid leukemia. Blood. 2020;135(26):2337–2353.
   PubMed Web of Science ®Google Scholar
• Kim T, Tyndel MS, Zhang Z, et al. Exome sequencing reveals DNMT3A and ASXL1 variants associate with progression of chronic myeloid leukemia after tyrosine kinase inhibitor therapy. Leuk Res. 2017;59:142–148.
   PubMed Web of Science ®Google Scholar
• Li S, Mason CE, Melnick A. Genetic and epigenetic heterogeneity in acute myeloid leukemia. Curr Opin Genet Dev. 2016;36:100–106.
   PubMed Web of Science ®Google Scholar
• Genovese G, Kähler AK, Handsaker RE, et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014;371(26):2477–2487.
   PubMed Web of Science ®Google Scholar
• Steensma DP, Bejar R, Jaiswal S, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126(1):9–16.
   PubMed Web of Science ®Google Scholar
• Li X, Cen J, Wang Q, et al. Absence of DNMT3A gene mutation in chronic myeloid leukemia patients in blast crisis. Eur J Haematol. 2012;88(5):455–457.
   PubMed Web of Science ®Google Scholar
• Thomson DW, Shahrin NH, Wang PPS, et al. Aberrant RAG-mediated recombination contributes to multiple structural rearrangements in lymphoid blast crisis of chronic myeloid leukemia. Leukemia. 2020;34(8):2051–2063.
   PubMed Web of Science ®Google Scholar
• DiNardo CD, Cortes JE. Mutations in AML: prognostic and therapeutic implications. Hematology Am Soc Hematol Educ Program. 2016;2016(1):348–355.
   PubMedGoogle Scholar
• Makishima H, Jankowska AM, McDevitt MA, et al. CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations and additional chromosomal aberrations constitute molecular events in chronic myelogenous leukemia. Blood. 2011;117(21):e198–e206.
   PubMed Web of Science ®Google Scholar
• Zhao L-J, Wang Y-Y, Li G, et al. Functional features of RUNX1 mutants in acute transformation of chronic myeloid leukemia and their contribution to inducing murine full-blown leukemia. Blood. 2012;119(12):2873–2882.
   PubMed Web of Science ®Google Scholar
• Zhang S-J, Ma L-Y, Huang Q-H, et al. Gain-of-function mutation of GATA-2 in acute myeloid transformation of chronic myeloid leukemia. Proc Natl Acad Sci USA. 2008;105(6):2076–2081.
   PubMed Web of Science ®Google Scholar
• Yamamoto K, Tsuzuki S, Minami Y, et al. Functionally deregulated AML1/RUNX1 cooperates with BCR-ABL to induce a blastic phase-like phenotype of chronic myelogenous leukemia in mice. PLoS One. 2013;8(9):e74864.
   PubMed Web of Science ®Google Scholar
• Boultwood J, Perry J, Zaman R, et al. High-density single nucleotide polymorphism array analysis and ASXL1 gene mutation screening in chronic myeloid leukemia during disease progression. Leukemia. 2010;24(6):1139–1145.
   PubMed Web of Science ®Google Scholar
• Magistroni V, Mauri M, D'Aliberti D, et al. De novo UBE2A mutations are recurrently acquired during chronic myeloid leukemia progression and interfere with myeloid differentiation pathways. Haematologica. 2019;104(9):1789–1797.
   PubMed Web of Science ®Google Scholar
• Grossmann V, Kohlmann A, Zenger M, et al. A deep-sequencing study of chronic myeloid leukemia patients in blast crisis (BC-CML) detects mutations in 76.9% of cases. Leukemia. 2011;25(3):557–560.
   PubMed Web of Science ®Google Scholar
• Sklarz L-M, Wittke C, Krohn S, et al. Genetic mutations in a patient with chronic myeloid leukemia showing blast crisis 10 years after presentation. Anticancer Res. 2018;38(7):3961–3966.
   PubMed Web of Science ®Google Scholar
• Huang Y, Zheng J, Hu JD, et al. Discovery of somatic mutations in the progression of chronic myeloid leukemia by whole-exome sequencing. Genet Mol Res. 2014;13(1):945–953.
   PubMed Web of Science ®Google Scholar
• Adnan AS, Dufva O, Ianevski A, et al. RUNX1 mutations in blast-phase chronic myeloid leukemia associate with distinct phenotypes, transcriptional profiles, and drug responses. Leukemia. 2020:1–13. doi:10.1038/s41375-020-01011-5
   Web of Science ®Google Scholar
• Mullighan CG, Miller CB, Radtke I, et al. BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. Nature. 2008;453(7191):110–114.
   PubMed Web of Science ®Google Scholar
• Mullighan CG, Su X, Zhang J, et al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med. 2009;360(5):470–480.
   PubMed Web of Science ®Google Scholar
• Marke R, Leeuwen FN, van, Scheijen B. The many faces of IKZF1 in B-cell precursor acute lymphoblastic leukemia. 1. Haematologica. 2018;103(4):565–574.
   PubMed Web of Science ®Google Scholar
• Rampal R, Figueroa ME. Wilms tumor 1 mutations in the pathogenesis of acute myeloid leukemia. Haematologica. 2016;101(6):672–679.
   PubMed Web of Science ®Google Scholar
• Ahuja H, Bar-Eli M, Arlin Z, et al. The spectrum of molecular alterations in the evolution of chronic myelocytic leukemia. J Clin Invest. 1991;87(6):2042–2047.
   PubMed Web of Science ®Google Scholar
• Nakai H, Misawa S, Toguchida J, et al. Frequent p53 gene mutations in blast crisis of chronic myelogenous leukemia, especially in myeloid crisis harboring loss of a chromosome 17p. Cancer Res. 1992;52(23):6588–6593.
   PubMed Web of Science ®Google Scholar
• Mersch J, Jackson M, Park M, et al. Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian. Cancer. 2015;121(2):269–275.
   PubMed Web of Science ®Google Scholar
• Dong Y, Zhao X, Feng X, et al. SETD2 mutations confer chemoresistance in acute myeloid leukemia partly through altered cell cycle checkpoints. Leukemia. 2019;33(11):2585–2598.
   PubMed Web of Science ®Google Scholar
• Li J, Duns G, Westers H, et al. SETD2: an epigenetic modifier with tumor suppressor functionality. Oncotarget. 2016;7(31):50719–50734.
   PubMedGoogle Scholar
• Mancini M, Santis SD, Monaldi C, et al. SETD2 loss of function is a recurrent event in advanced-phase chronic myeloid leukemia. Blood. 2017;130:43.
   Web of Science ®Google Scholar
• Krzyzewska IM, Maas SM, Henneman P, et al. A genome-wide DNA methylation signature for SETD1B-related syndrome. Clin Epigenetics. 2019;11(1):156.
   PubMed Web of Science ®Google Scholar
• Ochi Y, Yoshida K, Huang Y-J, et al. Molecular profiling of blastic transformation in chronic myeloid leukemia. Blood. 2018;132(Supplement 1):1725.
   PubMedGoogle Scholar
• Tiacci E, Grossmann V, Martelli MP, et al. The corepressors BCOR and BCORL1: two novel players in acute myeloid leukemia. Haematologica. 2012;97(1):3–5.
   PubMed Web of Science ®Google Scholar
• Damm F, Chesnais V, Nagata Y, et al. BCOR and BCORL1 mutations in myelodysplastic syndromes and related disorders. Blood. 2013;122(18):3169–3177.
   PubMed Web of Science ®Google Scholar
• Cao Q, Gearhart MD, Gery S, et al. BCOR regulates myeloid cell proliferation and differentiation. Leukemia. 2016;30(5):1155–1165.
   PubMed Web of Science ®Google Scholar
• Bergink S, Jentsch S. Principles of ubiquitin and SUMO modifications in DNA repair. Nature. 2009;458(7237):461–467.
   PubMed Web of Science ®Google Scholar
• Williams RT, Sherr CJ. BCR–ABL and CDKN2A: a dropped connection. Nat Rev Cancer. 2008;8(7):563.
   PubMed Web of Science ®Google Scholar
• Wang Y, Wu N, Liu D, et al. Recurrent fusion genes in leukemia: an attractive target for diagnosis and treatment. Curr Genomics. 2017;18(5):378–384.
   PubMed Web of Science ®Google Scholar
• Salem A, Loghavi S, Tang G, et al. Myeloid neoplasms with concurrent BCR-ABL1 and CBFB rearrangements: a series of 10 cases of a clinically aggressive neoplasm. Am J Hematol. 2017;92(6):520–528.
   PubMed Web of Science ®Google Scholar
• Mitani K, Ogawa S, Tanaka T, et al. Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia. Embo J. 1994;13(3):504–510.
   PubMed Web of Science ®Google Scholar
• Paquette RL, Nicoll J, Chalukya M, et al. Frequent EVI1 translocations in myeloid blast crisis CML that evolves through tyrosine kinase inhibitors. Cancer Genet. 2011;204(7):392–397.
   PubMed Web of Science ®Google Scholar
• Yin CC, Cortes J, Barkoh B, et al. t(3;21)(q26;q22) in myeloid leukemia: an aggressive syndrome of blast transformation associated with hydroxyurea or antimetabolite therapy. Cancer. 2006;106(8):1730–1738.
   PubMed Web of Science ®Google Scholar
• Najfeld V, Wisch N, Mascarenhas J, et al. Development of t(8;21) and RUNX1-RUNX1T1 in the Philadelphia-positive clone of a patient with chronic myelogenous leukemia: additional evidence for multiple steps involved in disease progression. Cancer Genet. 2011;204(3):165–170.
   PubMed Web of Science ®Google Scholar
• Wang W, Tang G, Cortes JE, et al. Chromosomal rearrangement involving 11q23 locus in chronic myelogenous leukemia: a rare phenomenon frequently associated with disease progression and poor prognosis. J Hematol Oncol. 2015;8:32.
   PubMed Web of Science ®Google Scholar
• Lilljebjörn H, Ågerstam H, Orsmark-Pietras C, et al. RNA-seq identifies clinically relevant fusion genes in leukemia including a novel MEF2D/CSF1R fusion responsive to imatinib. Leukemia. 2014;28(4):977–979.
   PubMed Web of Science ®Google Scholar
• Jain P, Kanagal-Shamanna R, Kantarjian HM, et al. Pattern of mutational changes in patients with chronic phase CML who are treated with frontline TKI and transform to blast phase CML. Blood. 2017;130:4172–4172.
   Web of Science ®Google Scholar
• Sokal JE, Cox EB, Baccarani M, et al. Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood. 1984;63(4):789–799.
   PubMed Web of Science ®Google Scholar
• Hasford J, Pfirrmann M, Hehlmann R, et al. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group. J Natl Cancer Inst. 1998;90(11):850–858.
   PubMedGoogle Scholar
• Hasford J, Baccarani M, Hoffmann V, et al. Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood. 2011;118(3):686–692.
   PubMed Web of Science ®Google Scholar
• Pfirrmann M, Baccarani M, Saussele S, et al. Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia. Leukemia. 2016;30(1):48–56.
   PubMed Web of Science ®Google Scholar
• Hu B, Savani BN. Impact of risk score calculations in choosing front-line tyrosine kinase inhibitors for patients with newly diagnosed chronic myeloid leukemia in the chronic phase. Eur J Haematol. 2014;93(3):179–186.
   PubMed Web of Science ®Google Scholar
• Suttorp M, Glauche I, Salas DG, et al. Scoring systems for predicting outcome of chronic myeloid leukemia in adults are poorly informative in pediatric patients treated with imatinib. Blood. 2013;122(21):2725–2725.
   Google Scholar
• Buesche G, Ganser A, Schlegelberger B, et al. Marrow fibrosis and its relevance during imatinib treatment of chronic myeloid leukemia. Leukemia. 2007;21(12):2420–2427.
   PubMed Web of Science ®Google Scholar
• Fabarius A, Kalmanti L, Dietz CT, et al. Impact of unbalanced minor route versus major route karyotypes at diagnosis on prognosis of CML. Ann Hematol. 2015;94(12):2015–2024.
   PubMed Web of Science ®Google Scholar
• Hehlmann R, Voskanyan A, Lauseker M, et al. High-risk additional chromosomal abnormalities at low blast counts herald death by CML. Leukemia. 2020;34(8):2074–2086.
   PubMed Web of Science ®Google Scholar
• Estey EH. Acute myeloid leukemia: 2019 update on risk-stratification and management. Am J Hematol. 2018;93(10):1267–1291.
   PubMed Web of Science ®Google Scholar
• Herold T, Rothenberg-Thurley M, Grunwald VV, et al. Validation and refinement of the revised 2017 European LeukemiaNet genetic risk stratification of acute myeloid leukemia. Leukemia. 2020;34(12):3161–3172.
   PubMed Web of Science ®Google Scholar
• Ng KP, Hillmer AM, Chuah CTH, et al. A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer. Nat Med. 2012;18(4):521–528.
   PubMed Web of Science ®Google Scholar
• Augis V, Airiau K, Josselin M, et al. A single nucleotide polymorphism in cBIM is associated with a slower achievement of major molecular response in chronic myeloid leukaemia treated with imatinib. PLoS One. 2013;8(11):e78582.
   PubMed Web of Science ®Google Scholar
• Than H, Lye WK, Sng C, et al. BIM deletion polymorphism profiling complements prognostic values of risk scores in imatinib-treated Asian chronic myeloid leukemia patients. Leuk Lymphoma. 2019;60(1):234–237.
   PubMed Web of Science ®Google Scholar
• Park J-H, Woo YM, Youm EM, et al. HMGCLL1 is a predictive biomarker for deep molecular response to imatinib therapy in chronic myeloid leukemia. Leukemia. 2019;33(6):1439–1450.
   PubMed Web of Science ®Google Scholar
• Abdel-Wahab O, Levine RL. Mutations in epigenetic modifiers in the pathogenesis and therapy of acute myeloid leukemia. Blood. 2013;121(18):3563–3572.
   PubMed Web of Science ®Google Scholar
• Fathi AT, Abdel-Wahab O. Mutations in epigenetic modifiers in myeloid malignancies and the prospect of novel epigenetic-targeted therapy. Adv Hematol. 2012;2012:469592.
   PubMedGoogle Scholar
• Marum JE, Yeung DT, Purins L, et al. ASXL1 and BIM germ line variants predict response and identify CML patients with the greatest risk of imatinib failure. Blood Adv. 2017;1(18):1369–1381.
   PubMed Web of Science ®Google Scholar
• Wu W, Xu N, Zhou X, et al. Integrative genomic analysis reveals cancer-associated gene mutations in chronic myeloid leukemia patients with resistance or intolerance to tyrosine kinase inhibitor. Onco Targets Ther. 2020;13:8581–8591.
   PubMed Web of Science ®Google Scholar
• Issa GC, Kantarjian HM, Gonzalez GN, et al. Clinical and molecular characterization of clonal chromosomal abnormalities appearing in philadelphia-negative metaphases of chronic phase CML. Blood. 2017;130(Supplement 1):47.
   PubMed Web of Science ®Google Scholar
• Jaiswal S, Natarajan P, Silver AJ, et al. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N Engl J Med. 2017;377(2):111–121.
   PubMed Web of Science ®Google Scholar
• Jain P, Kantarjian H, Boddu PC, et al. Analysis of cardiovascular and arteriothrombotic adverse events in chronic-phase CML patients after frontline TKIs. Blood Adv. 2019;3(6):851–861.
   PubMed Web of Science ®Google Scholar
• Hadzijusufovic E, Hoermann G, Herndlhofer S, et al. Cardiovascular scoring and age-related mutations predict the occurrence of adverse vascular events in CML patients during nilotinib therapy. Blood. 2017;130:1619.
   Web of Science ®Google Scholar
• Radivoyevitch T, Weaver D, Hobbs B, et al. Do persons with chronic myeloid leukaemia have normal or near normal survival? Leukemia. 2020;34(2):333–335.
   PubMed Web of Science ®Google Scholar
• Pemovska T, Kontro M, Yadav B, et al. Individualized systems medicine strategy to tailor treatments for patients with chemorefractory acute myeloid leukemia. Cancer Discov. 2013;3(12):1416–1429.
   PubMed Web of Science ®Google Scholar
• Swords RT, Azzam D, Al-Ali H, et al. Ex-vivo sensitivity profiling to guide clinical decision making in acute myeloid leukemia: a pilot study. Leuk Res. 2018;64:34–41.
   PubMed Web of Science ®Google Scholar
• Andersson EI, Pützer S, Yadav B, et al. Discovery of novel drug sensitivities in T-PLL by high-throughput ex vivo drug testing and mutation profiling. Leukemia. 2018;32(3):774–787.
   PubMed Web of Science ®Google Scholar
• Dietrich S, Oleś M, Lu J, et al. Drug-perturbation-based stratification of blood cancer. J Clin Invest. 2018;128(1):427–445.
   PubMed Web of Science ®Google Scholar
• Zhang H, Nakauchi Y, Köhnke T, et al. Integrated analysis of patient samples identifies biomarkers for venetoclax efficacy and combination strategies in acute myeloid leukemia. Nat Cancer. 2020;1(8):826–839.
   PubMedGoogle Scholar
• Pietarinen PO, Pemovska T, Kontro M, et al. Novel drug candidates for blast phase chronic myeloid leukemia from high-throughput drug sensitivity and resistance testing. Blood Cancer J. 2015;5:e309.
   PubMed Web of Science ®Google Scholar
• Pemovska T, Johnson E, Kontro M, et al. Axitinib effectively inhibits BCR-ABL1(T315I) with a distinct binding conformation. Nature. 2015;519(7541):102–105.
   PubMed Web of Science ®Google Scholar
• Simon L, Lavallée V-P, Bordeleau M-E, et al. Chemogenomic landscape of RUNX1-mutated AML reveals importance of RUNX1 allele dosage in genetics and glucocorticoid sensitivity. Clin Cancer Res. 2017;23(22):6969–6981.
   PubMed Web of Science ®Google Scholar
• Fuka G, Kantner H-P, Grausenburger R, et al. Silencing of ETV6/RUNX1 abrogates PI3K/AKT/mTOR signaling and impairs reconstitution of leukemia in xenografts. Leukemia. 2012;26(5):927–933.
   PubMed Web of Science ®Google Scholar
• Imai N, Shikami M, Miwa H, et al. t(8;21) acute myeloid leukaemia cells are dependent on vascular endothelial growth factor (VEGF)/VEGF receptor type2 pathway and phosphorylation of Akt. Br J Haematol. 2006;135(5):673–682.
   PubMed Web of Science ®Google Scholar
• Mill CP, Fiskus W, DiNardo CD, et al. RUNX1-targeted therapy for AML expressing somatic or germline mutation in RUNX1. Blood. 2019;134(1):59–73.
   PubMed Web of Science ®Google Scholar
• Danylesko I, Jacoby E, Yerushalmi R, et al. Remission of acute myeloid leukemia with t(8;21) following CD19 CAR T-cells. Leukemia. 2020;34(7):1939–1942.
   PubMed Web of Science ®Google Scholar
• Tauer J, Kronnie G. t, Ekici A, et al. Copy number variations and IKZF1 mutations in pediatric CML. Blood. 2013;122(21):1473.
   Web of Science ®Google Scholar
• Churchman ML, Low J, Qu C, et al. Efficacy of retinoids in IKZF1-mutated BCR-ABL1 acute lymphoblastic leukemia. Cancer Cell. 2015;28(3):343–356.
   PubMed Web of Science ®Google Scholar
• Yang H, Kurtenbach S, Guo Y, et al. Gain of function of ASXL1 truncating protein in the pathogenesis of myeloid malignancies. Blood. 2018;131(3):328–341.
   PubMed Web of Science ®Google Scholar
• Bykov VJN, Eriksson SE, Bianchi J, et al. Targeting mutant p53 for efficient cancer therapy. Nat Rev Cancer. 2018;18(2):89–102.
   PubMed Web of Science ®Google Scholar
• Sanz G, Singh M, Peuget S, et al. Inhibition of p53 inhibitors: progress, challenges and perspectives. J Mol Cell Biol. 2019;11(7):586–599.
   PubMed Web of Science ®Google Scholar
• Li CH, Chen Y. Targeting EZH2 for cancer therapy: progress and perspective. Curr Protein Pept Sci. 2015;16(6):559–570.
   PubMed Web of Science ®Google Scholar
• Jones BA, Varambally S, Arend RC. Histone methyltransferase EZH2: a therapeutic target for ovarian cancer. Mol Cancer Ther. 2018;17(3):591–602.
   PubMed Web of Science ®Google Scholar
• Liu X, Gong Y. Isocitrate dehydrogenase inhibitors in acute myeloid leukemia. Biomark Res. 2019;7:22.
   PubMed Web of Science ®Google Scholar
• Chapuis AG, Egan DN, Bar M, et al. T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant. Nat Med. 2019;25(7):1064–1072.
   PubMed Web of Science ®Google Scholar
• Dao T, Yan S, Veomett N, et al. Targeting the intracellular WT1 oncogene product with a therapeutic human antibody. Sci Transl Med. 2013;5(176):176ra33.
   PubMed Web of Science ®Google Scholar
• Buscarlet M, Provost S, Zada YF, et al. DNMT3A and TET2 dominate clonal hematopoiesis and demonstrate benign phenotypes and different genetic predispositions. Blood. 2017;130(6):753–762.
   PubMed Web of Science ®Google Scholar
• Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. New Eng J Med. 2013;368:2059–2074.
   PubMed Web of Science ®Google Scholar
• Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374(23):2209–2221.
   PubMed Web of Science ®Google Scholar
• Haferlach T, Nagata Y, Grossmann V, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia. 2014;28(2):241–247.
   PubMed Web of Science ®Google Scholar