[...]... Contents 1. 1 Introduction 1 1.2 The 19 th Century 1. 2 .1 Clinical Aspects and Biology 1. 2.2 Therapy 2 2 4 1. 3 First Half of the 20th Century 1. 3 .1 Clinical Aspects and Biology 1. 3.2 Therapy 4 4 5 1. 4 Latter Half of the 20th Century 1. 4 .1 Biology 1. 4.2 Therapy 5 5 5 1. 5... (bcr) on chromosome 22 19 85 Identification of the BCR-ABL fusion gene and p 210 -Bcr-Abl 19 90 Demonstration that the BCR-ABL gene can induce a CML-like disease in mice 19 96 Demonstration of selective blocking of Bcr-Abl kinase activity 19 98 Blocking Bcr-Abl kinase activity reverses features of CML 20 01 Recognition of nonrandom mutations in the Abl kinase domain 1. 2 The 19 th Century 1. 2 .1 Clinical Aspects... Tables 1. 1 and 1. 2) Table 1. 2 Milestones in the treatment of CML 18 65 First documented use of arsenic to treat CML (Fowler’s solution) 18 95 Discovery of x-irradiation and subsequent use in CML 19 46 First effective chemotherapy for leukemia – nitrogen mustard 19 56 Busulfan 19 75 Hydroxyurea 19 79 Identical twin transplants 19 81 Allografting with sibling donors 19 82 Clinical use of interferon-alfa 19 84 Sokal’s... S, Buchdunger E et al (19 96) Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells Nat Med 2:5 61 566 12 Chapter 1 · Chronic Myeloid Leukemia – A Brief History Eckhardt S, Sellei C, Horvath IP, Institorisz L (19 63) Effect of 1, 6-dibromo -1 , 6-dideoxy-D-mannitol on chronic granulocytic leukemia Cancer Chemother Rep 33:57– 71 Ehrlich P (18 91) Farbenanalytische... preferential inhibition of Ph1-positive leukemia cell growth Blood 80 :13 30 13 38 Piller G (19 93) The history of leukemia: a personal perspective Blood Cells 19 :5 21 529 Piller GJ (20 01) Leukaemia – a brief historical review from ancient times to 19 50 Br J Haematol 11 2:282–292 Pusey WA (19 02) Report of cases treated with Roentgen rays JAMA 38: 911 – 919 Reddy EP, Smith MJ, Srinivasan A (19 83) Nucleotide sequence... Baltimore D (19 86) The chronic myelogenous leukemia specific p 210 protein is the product of the bcr/abl hybrid gene Science 223: 212 – 214 Beran M, Cao X, Estrov Z et al (19 98) Selective inhibition of cell proliferation and BCR-ABL phosphorylation in acute lymphoblastic leukemia cells expressing Mr 19 0 000 BCR-ABL protein by a tyrosine kinase inhibitor (CGP-5 714 8) Clin Cancer Res 4 :16 61 16 72 Bernards... and hematological remissions (Lawrence et al 19 39) but was not as effective as external x-rays in reducing organomegaly (Reinhard et al 19 46) 1. 4 Latter Half of the 20th Century 1. 4 .1 Biology Though Boveri had predicted as early as 19 14 that human malignancies would prove to have a genetic basis (Boveri 19 14), it was not until technology for examining human chromosomes developed sufficiently in the 19 50s... imatinib with IFN/Ara-C 18 46 First diagnosis of leukemia in a live patient 2004 18 80s Development of methods for staining blood cells First clinical use of second-generation TK inhibitors 19 51 Dameshek introduces the concept of myeloproliferative disorders 19 60 Identification of the Philadelphia chromosome (22q-) 19 73 Recognition of the reciprocal nature of the (9;22) translocation 19 84 Description of... France in 18 27 (Velpeau 18 27), although it is likely that forms of leukemia had been recognized as early as 18 11 (Piller 19 93, 20 01) This was followed by the observations of Barth and Donne (Donne 18 42) and of Craigie (Craigie 18 45) Nevertheless, the definition of leukemia as a distinct entity is attributed to the virtually simultaneous autopsy reports in 18 45 by John Hughes Bennett of a 28-year-old slater... Virchow in Berlin of a 50-year-old cook (Bennett 18 45; Virchow 18 46, 18 53) (Fig 1. 1) Both patients had been unwell for 1. 5 to 2 years and their condition had progressively worsened with increasing weakness, bleeding, and other problems In both cases the remarkable features at autopsy were the large size of the spleen and the consistency of the blood, a 1. 2 · The 19 th Century 3 Fig 1. 1 Front pages of the . Hospital Bethesda, MD 20892 Du Cane Road USA London W12 0NN UK ISBN -1 0 3-5 4 0-3 450 5 -1 Springer Berlin Heidelberg New York ISBN -1 3 97 8-3 -5 4 0-3 450 5-3 Springer Berlin Heidelberg New York Library of. USA Contents 1. 1 Introduction 1 1.2 The 19 th Century 2 1. 2 .1 Clinical Aspects and Biology 2 1. 2.2 Therapy 4 1. 3 First Half of the 20th Century 4 1. 3 .1 Clinical Aspects and Biology 4 1. 3.2 Therapy 5 1. 4. the 20th Century 5 1. 4 .1 Biology 5 1. 4.2 Therapy 5 1. 5 Last Quarter of the 20th Century 7 1. 5 .1 Biology 7 1. 5.2 Therapy 8 1. 5.3 Development of Imatinib Mesylate . 10 References 11 Abstract. Leukemia