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Diagnosis and classification of the risk

    Gabriele Gugliotta

    Gabriele Gugliotta is a Hematologist at the University Hospital of Bologna (Italy). His main research field is chronic myeloid leukemia, where he is collaborating in many clinical and biological studies. He is now conducting his PhD in biomedical sciences on the characterization of chronic myeloid leukemia stem cells.

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    ,
    Fausto Castagnetti

    Fausto Castagnetti’s main scientific interest is chronic myeloid leukemia. He is the author or co-author of more than 50 scientific publications and more than 200 abstracts of presentations at international congresses. He is involved in several investigator-initiated and company-sponsored clinical and biologic studies and a Member of the GIMEMA CML Working Party and Member of the “European Investigators on CML” (EiCML) Group.

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    ,
    Francesca Palandri

    Francesca Palandri is an Assistant Professor at the Department of Hematology and Medical Oncology, “L. and A. Seragnoli”, S. Orsola-Malpighi Hospital, of the University of Bologna in Italy. Her main research interests lie in the areas of clinical management of chronic myeloproliferative neoplasms, minimal residual disease in CML, and the efficacy and safety of tyrosine kinase inhibitors (TKIs) in the long-term and post-transplantation CML setting.

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    ,
    Michele Baccarani

    Institute of Hematology and Oncology, Universita di Bologna, Bologna, Italy

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    &
    Gianantonio Rosti

    Department of Hematology/Oncology “L. and A. Seràgnoli,” St. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti, 9-40138 Bologna, Italy

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    Published Online:22 Jul 2013https://doi.org/10.2217/ebo.13.171
    Abstract:

    Chronic myeloid leukemia is a clonal stem cell disorder characterized by the acquisition of an oncogenic BCR-ABL fusion protein that leads to the proliferation of granulocytic elements at all stages of differentiation [1,2]. The BCR-ABL fusion gene is the result of a reciprocal translocation t(9;22)(q34;q11), also known as the Philadelphia chromosome, first discovered by Nowell and Hungerford in 1960 [3–5].

    References

    • 1  Tefferi A , Vardiman JW . Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms . Leukemia 22 (1) , 14 – 22 (2008) .
      Medline CASGoogle Scholar
    • 2  Hehlmann R , Hochhaus A , Baccarani M . Chronic myeloid leukaemia . Lancet 370 (9584) , 342 – 350 (2007) .
      Medline CASGoogle Scholar
    • 3  Nowell PC , Hungerford DA . Chromosome studies on normal and leukemic human leukocytes . J. Natl Cancer Inst. 25 , 85 – 109 (1960) .
      Medline CASGoogle Scholar
    • 4  Geary CG . The story of chronic myeloid leukaemia . Br. J. Haematol. 110 (1) , 2 – 11 (2000) .
      Medline CASGoogle Scholar
    • 5  Rowley JD . Letter: a new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining . Nature 243 (5405) , 290 – 293 (1973) .
      Medline CASGoogle Scholar
    • 6  Savage DG , Szydlo RM , Goldman JM . Clinical features at diagnosis in 430 patients with chronic myeloid leukaemia seen at a referral centre over a 16-year period . Br. J. Haematol. 96 (1) , 111 – 116 (1997) .
      Medline CASGoogle Scholar
    • 7  Greer JP . Wintrobe’s Clinical Hematology. Lippincott Williams & Wilkins, PA, USA (2008) .
      Google Scholar
    • 8  Baccarani M , Saglio G , Goldman J et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet . Blood 108 (6) , 1809 – 1820 (2006) .
      Medline CASGoogle Scholar
    • 9  Kantarjian HM , Keating MJ , Talpaz M et al. Chronic myelogenous leukemia in blast crisis. Analysis of 242 patients . Am. J. Med. 83 (3) , 445 – 454 (1987) .
      Medline CASGoogle Scholar
    • 10  Spiers AS , Bain BJ , Turner JE . The peripheral blood in chronic granulocytic leukaemia. Study of 50 untreated Philadelphia-positive cases . Scand. J. Haematol. 18 (1) , 25 – 38 (1977) .
      Medline CASGoogle Scholar
    • 11  Georgii A , Vykoupil KF , Buhr T et al. Chronic myeloproliferative disorders in bone marrow biopsies . Pathol. Res. Pract. 186 (1) , 3 – 27 (1990) .
      Medline CASGoogle Scholar
    • 12  Thiele J , Kvasnicka HM , Schmitt-Graeff A et al. Bone marrow features and clinical findings in chronic myeloid leukemia – a comparative, multicenter, immunohistological and morphometric study on 614 patients . Leuk. Lymphoma 36 (3–4) , 295 – 308 (2000) .
      Medline CASGoogle Scholar
    • 13  Holdrinet RS , Pennings A , Van Egmond J , Wessels JM , Haanen C . DNA-flow cytometry of blood and bone marrow in chronic myelogenous leukemia . Acta Haematol. 69 (2) , 98 – 105 (1983) .
      Medline CASGoogle Scholar
    • 14  Amiel A , Yarkoni S , Fejgin M et al. Clinical detection of BCR-ABL fusion by in situ hybridization in chronic myelogenous leukemia . Cancer Genet. Cytogenet. 65 (1) , 32 – 34 (1993) .
      Medline CASGoogle Scholar
    • 15  Testoni N , Marzocchi G , Luatti S et al. Chronic myeloid leukemia: a prospective comparison of interphase fluorescence in situ hybridization and chromosome banding analysis for the definition of complete cytogenetic response: a study of the GIMEMA CML WP . Blood 114 (24) , 4939 – 4943 (2009) .
      Medline CASGoogle Scholar
    • 16  Bentz M , Cabot G , Moos M et al. Detection of chimeric BCR-ABL genes on bone marrow samples and blood smears in chronic myeloid and acute lymphoblastic leukemia by in situ hybridization . Blood 83 (7) , 1922 – 1928 (1994) .
      Medline CASGoogle Scholar
    • 17  Hagemeijer A , Buijs A , Smit E et al. Translocation of BCR to chromosome 9: a new cytogenetic variant detected by FISH in two Ph-negative, BCR-positive patients with chronic myeloid leukemia . Genes Chromos. Cancer 8 (4) , 237 – 245 (1993) .
      Medline CASGoogle Scholar
    • 18  Kurzrock R , Gutterman JU , Talpaz M . The molecular genetics of Philadelphia chromosome-positive leukemias . N. Engl. J. Med. 319 (15) , 990 – 998 (1988) .
      Medline CASGoogle Scholar
    • 19  Mcclure JS , Litz CE . Chronic myelogenous leukemia: molecular diagnostic considerations . Hum. Pathol. 25 (6) , 594 – 597 (1994) .
      Medline CASGoogle Scholar
    • 20  Pane F , Frigeri F , Sindona M et al. Neutrophilic-chronic myeloid leukemia: a distinct disease with a specific molecular marker (BCR/ABL with C3/A2 junction) . Blood 88 (7) , 2410 – 2414 (1996) .
      Medline CASGoogle Scholar
    • 21  Sokal JE , Cox EB , Baccarani M et al. Prognostic discrimination in ‘good-risk’ chronic granulocytic leukemia . Blood 63 (4) , 789 – 799 (1984) .
      Medline CASGoogle Scholar
    • 22  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. 90 (11) , 850 – 858 (1998) .
      Medline CASGoogle Scholar
    • 23  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 118 (3) , 686 – 692 (2011) .
      Medline CASGoogle Scholar
    • 24  No authors listed. Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. The Italian Cooperative Study Group on Chronic Myeloid Leukemia . N. Engl. J. Med. 330 (12) , 820 – 825 (1994) .
      MedlineGoogle Scholar
    • 25  Allan NC , Richards SM , Shepherd PC . UK Medical Research Council randomised, multicentre trial of interferon-α n1 for chronic myeloid leukaemia: improved survival irrespective of cytogenetic response. The UK Medical Research Council’s working parties for therapeutic trials in adult leukaemia . Lancet 345 (8962) , 1392 – 1397 (1995) .
      Medline CASGoogle Scholar
    • 26  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. 349 (15) , 1423 – 1432 (2003) .
      Medline CASGoogle Scholar
    • 27  Hochhaus A , O’Brien SG , Guilhot F et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia . Leukemia 23 (6) , 1054 – 1061 (2009) .
      Medline CASGoogle Scholar
    • 28  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. 355 (23) , 2408 – 2417 (2006) .
      Medline CASGoogle Scholar
    • 29  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 26 (10) , 2302 (2012) .
      Google Scholar
    • 30  Bonifazi F , De Vivo A , Rosti G et al. Testing Sokal’s and the new prognostic score for chronic myeloid leukaemia treated with α-interferon. Italian Cooperative Study Group on Chronic Myeloid Leukaemia . Br. J. Haematol. 111 (2) , 587 – 595 (2000) .
      Medline CASGoogle Scholar
    • 31  Kantarjian H , Shah NP , Hochhaus A et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia . N. Engl. J. Med. 362 (24) , 2260 – 2270 (2010) .
      Medline CASGoogle Scholar
    • 32  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. 29 (12) , 1634 – 1642 (2011) .
      Medline CASGoogle Scholar
    • 33  Gugliotta G , Castagnetti F , Palandri F et al. Frontline imatinib treatment of chronic myeloid leukemia: no impact of age on outcome, a survey by the GIMEMA CML Working Party . Blood 117 (21) , 5591 – 5599 (2011) .
      Medline CASGoogle Scholar
    • 34  Preudhomme C , Guilhot J , Nicolini FE et al. Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia . N. Engl. J. Med. 363 (26) , 2511 – 2521 (2010) .
      Medline CASGoogle Scholar
    • 35  Deenik W , Van Der Holt B , Verhoef GE et al. Dose-finding study of imatinib in combination with intravenous cytarabine: feasibility in newly diagnosed patients with chronic myeloid leukemia . Blood 111 (5) , 2581 – 2588 (2008) .
      Medline CASGoogle Scholar
    • 36  Simonsson B , Gedde-Dahl T , Markevarn B et al. Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia . Blood 118 (12) , 3228 – 3235 (2011) .
      Medline CASGoogle Scholar
    • 37  Baccarani M , Cortes J , Pane F et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet . J. Clin. Oncol. 27 (35) , 6041 – 6051 (2009) .
      Medline CASGoogle Scholar
    • 38  Marin D , Ibrahim AR , Goldman JM . European Treatment and Outcome Study (EUTOS) score for chronic myeloid leukemia still requires more confirmation . J. Clin. Oncol. 29 (29) , 3944 – 3945 (2011) .
      MedlineGoogle Scholar
    • 39  Jabbour E , Cortes J , Nazha A et al. EUTOS score is not predictive for survival and outcome in patients with early chronic phase chronic myeloid leukemia treated with tyrosine kinase inhibitors: a single institution experience . Blood 119 (19) , 4524 – 4526 (2012) .
      Medline CASGoogle Scholar
    • 40  Luatti S , Castagnetti F , Marzocchi G et al. Additional chromosomal abnormalities in Philadelphia-positive clone: adverse prognostic influence on frontline imatinib therapy: a GIMEMA Working Party on CML analysis . Blood 120 (4) , 761 – 767 (2012) .
      Medline CASGoogle Scholar
    • 41  Fabarius A , Leitner A , Hochhaus A et al. Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV . Blood 118 (26) , 6760 – 6768 (2011) .
      Medline CASGoogle Scholar
    • 42  Castagnetti F , Testoni N , Luatti S et al. Deletions of the derivative chromosome 9 do not influence the response and the outcome of chronic myeloid leukemia in early chronic phase treated with imatinib mesylate: GIMEMA CML Working Party analysis . J. Clin. Oncol. 28 (16) , 2748 – 2754 (2010) .
      Medline CASGoogle Scholar
    • 43  Marzocchi G , Castagnetti F , Luatti S et al. Variant Philadelphia translocations: molecular–cytogenetic characterization and prognostic influence on frontline imatinib therapy, a GIMEMA Working Party on CML analysis . Blood 117 (25) , 6793 – 6800 (2011) .
      Medline CASGoogle Scholar
    • 44  Richebourg S , Eclache V , Perot C et al. Mechanisms of genesis of variant translocation in chronic myeloid leukemia are not correlated with ABL1 or BCR deletion status or response to imatinib therapy . Cancer Genet. Cytogenet. 182 (2) , 95 – 102 (2008) .
      Medline CASGoogle Scholar
    • 45  Graham SM , Vass JK , Holyoake TL , Graham GJ . Transcriptional analysis of quiescent and proliferating CD34+ human hemopoietic cells from normal and chronic myeloid leukemia sources . Stem Cells 25 (12) , 3111 – 3120 (2007) .
      Medline CASGoogle Scholar
    • 46  Oehler VG , Yeung KY , Choi YE , Bumgarner RE , Raftery AE , Radich JP . The derivation of diagnostic markers of chronic myeloid leukemia progression from microarray data . Blood 114 (15) , 3292 – 3298 (2009) .
      Medline CASGoogle Scholar
    • 47  Mcweeney SK , Pemberton LC , Loriaux MM et al. A gene expression signature of CD34+ cells to predict major cytogenetic response in chronic-phase chronic myeloid leukemia patients treated with imatinib . Blood 115 (2) , 315 – 325 (2010) .
      Medline CASGoogle Scholar
    • 48  Nowak D , Ogawa S , Muschen M et al. SNP array analysis of tyrosine kinase inhibitor-resistant chronic myeloid leukemia identifies heterogeneous secondary genomic alterations . Blood 115 (5) , 1049 – 1053 (2010) .
      Medline CASGoogle Scholar
    • 49  Tipping AJ , Deininger MW , Goldman JM , Melo JV . Comparative gene expression profile of chronic myeloid leukemia cells innately resistant to imatinib mesylate . Exp. Hematol. 31 (11) , 1073 – 1080 (2003) .
      Medline CASGoogle Scholar
    • 50  Cilloni D , Messa F , Gottardi E et al. Sensitivity to imatinib therapy may be predicted by testing Wilms tumor gene expression and colony growth after a short in vitro incubation . Cancer 101 (5) , 979 – 988 (2004) .
      Medline CASGoogle Scholar