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Article Number: EC2/2015/045


Topic: Clinical Research


Chronic Myeloid Leukaemia (CML) is a clonal disorder of a pluripotent stem cell characterized by the Philadelphia (Ph) chromosome. The Ph is a shortened chromosome 22 resulting from a reciprocal translocation between the BCR gene on chromosome 22 and the ABL gene on chromosome 9 (Mondal et al., 2006). The resulting overactive ABL tyrosine kinase appears to be responsible for uncontrolled myeloid cell proliferation (Hughes et al., 2006). Imatinib, also called Gliveec, is the first and most commonly used tyrosine kinase inhibitor (TKI) that inhibits by binding through ATP (adenosine triphosphate) onto the BCR-ABL fusion protein of which when absent the kinase leads to uncontrolled cell proliferation. The level of BCR-ABL mRNA can be used as a sensitive marker for disease progression (Hoffbrand et al., 2001). In approximately 5% of CML cases, patients present with a variant Ph chromosome in which the Ph chromosome is derived through rearrangements other than the classic t(9;22) (Hughes, et al., 2006). 
The aim of this study is to assess the response to therapy between classic chronic myeloid leukaemia patients and variant translocation chronic myeloid leukaemia patients.
Methods for monitoring treatment response include conventional cytogenetic analysis, Fluorescence in situ hybridization (FISH) and Quantitative PCR (polymerase chain reaction). BCR-ABL transcript levels quantified by PCR will be used to assess the response of therapy, which in turn influences the choice of clinical management.
The response in therapy will be monitored in patients with variant Ph translocations compared to patients with classical Ph translocation who have or have not responded to treatment.


    COMMENT - 1

  • Dr. AJIT V PANDYA (Viewer) 16th Nov 2015 - 5:29 PM
    Good morning from Dr. Ajit V Pandya form Ahmedabad ..India
    My questions / suggestion (s) are as follows…my email id is
    Watsapp no. 91 8905599852

    1. leukemia and this CML are same or different ? it possible to have same medicine if any ......can work for all types of cancers ?.........

  • COMMENT - 2

  • MLUNGISI PATRICK MSIBI (Author) 17th Nov 2015 - 11:35 AM
    Thank you for reading the article Dr Ajit V Pandya
    My responses to your questions are asd follows;
    1. Leukemia is different from Chronic myelogenous leukemia (CML) by the following; Leukemia is a proliferative white cell disorder in which the bone marrow produce increased numbers of immature or abnormal leukocytes in an uncontrolled and regulated manner. These suppress the production of normal blood cells. CML also known as chronic myeloid leukemia, is a myeloproliferative ( only the myeloid cell line affected) disorder characterized by increased proliferation of the granulocytic cell line without the loss of their capacity to differentiate. It accounts for 20% of all leukemias affecting adults.
    2. The is a wide range of treatment for the same ranging from gleevec, hydroxyuria and others and this is dependent on the type of blasts (immature cells produced), the exons in the genome affected (type of mutation) and other factors. The treatment may not be different. Therfore the treatment cannot work for all type of cancers.

  • COMMENT - 3

  • Michael Sello Seahloli (Viewer) 19th Nov 2015 - 2:28 AM
    This is a good article in general. However imatinib is a very toxic drug and the side effects management was not emphasized or explained especially management of neutropenia and thrombocytopenia.

  • COMMENT - 4

  • MLUNGISI PATRICK MSIBI (Author) 19th Nov 2015 - 5:01 PM
    Thank yo Michael
    The mechanisms by which CML affects normal hemopoiesis is understood. Displacement through the expanding clone, microenvironmental factors or inhibitory cytokines are responsible for the suppression of normal hematopoiesis resulting to neutropenia and thrombocytopenia. Not all CML cases are bicytopenic as stated, it depends on a number of factors.
    The focus of this article is looking diagnostic tools for monitoring the response to therapy on a double cohort study of patients (one with classic Philadelphia and the other with variants of CML). It was only relevant to emphasize on such if we were to evaluate adverse drug effects on Imatinib.
    I hope this is clarified.

  • COMMENT - 5

  • UGOCHI FELICIA EZENWELU (Viewer) 24th Nov 2015 - 5:57 AM
    This a good research study.
    Knowing that Imatinib is a toxic drug, evaluation of the toxic effect on the body like liver cells can also be very informative.

  • COMMENT - 6

  • MLUNGISI PATRICK MSIBI (Author) 25th Nov 2015 - 2:37 PM
    In response to your comment, the relevance of doing liver function tests (AST, ALP, LDH, GGT etc) would be done only to assess liver damage but required to determine baseline if your aim is to look at side effects of the chemotherapy. This is not relevant in this case since its aimed at evaluating the response to treatment (gleevec/ imatinib) in different types of CML

  • COMMENT - 7

  • Vinod Ramesh Gyanchandani (Viewer) 27th Nov 2015 - 4:55 PM

    In most of the prescription Index of various marketed drugs; recommended dose of Imatinib is 400 mg BD. Depending upn the toxicity tolerance of Imatinib by patients; few doctors prescribe 600 mg to 800 mg OD also; as few clinical trials were conducted on those lines too. wanted to know does the outcome of your article supports 600/800 mg also.