1887
Volume 2014, Issue 1
  • E-ISSN: 2223-506X

Abstract

Most cases of chronic myeloid leukemia (CML) are associated with the presence of fusion gene; a molecular anomaly that introduced targeting therapy to CML. This study was setup primarily to optimize the real-time quantification detection of transcripts, in order to pave the way for using this method as a diagnostic tool to support the clinical management of CML patients in Qatar.

A secondary objective was to evaluate the response of CML patients to Imatinib (IM) and exploit adaption of this technique as an indicator of emerging drug resistance reported in Qatar.

Peripheral blood (PB) samples from 26 CML patients receiving Imatinib, were analysed via serial Real-time quantitative polymerase chain reaction (RT-qPCR) to monitor the ratio of to normal transcripts. EuropeanLeukemia Net (ELN) 2006 and 2009 guidelines were employed to assess the molecular response to Imatinib.

For patients to be classified as optimal responders, major molecular response (MMR) had to be achieved by 18 months of treatment.1 Patients responding to Imatinib achieved major molecular response (MMR) during the 1st year of treatment; while patients who resisted Imatinib treatment did not achieve any molecular response within this time frame.

This was the first molecular study to evaluate the molecular response of CML patients (citizens and residents) to IM in Qatar.

Loading

Article metrics loading...

/content/journals/10.5339/connect.2014.24
2014-11-01
2019-08-18
Loading full text...

Full text loading...

/deliver/fulltext/connect/2014/1/connect.2014.24.html?itemId=/content/journals/10.5339/connect.2014.24&mimeType=html&fmt=ahah

References

  1. [1]. Shtivelman   E., , Lifshitz   B., , Gale   RP., , Canaani   E. . Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. . Nature . 1985; ;315: 6020 : 550– 554 .
    [Google Scholar]
  2. [2]. Melo   JV., , Chuah   C. . Resistance to imatinib mesylate in chronic myeloid leukaemia. . Cancer Lett . 2007; ;249: 2 : 121– 132 .
    [Google Scholar]
  3. [3]. Melo   JV. . The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype. . Blood . 1996; ;88: 7 : 2375– 2384 .
    [Google Scholar]
  4. [4]. Branford   S., , Hughes   T. . Diagnosis and monitoring of chronic myeloid leukemia by qualitative and quantitative RT-PCR. . Methods Mol Med . 2006; ;125: : 69– 92 .
    [Google Scholar]
  5. [5]. Cross   NC. . Standardisation of molecular monitoring for chronic myeloid leukaemia. . Best Pract Res Clin Haematol . 2009; ;22: 3 : 355– 365 .
    [Google Scholar]
  6. [6]. Baccarani   M., , Saglio   G., , Goldman   J., , Hochhaus   A., , Simonsson   B., , Appelbaum   F., , Apperley   J., , Cervantes   F., , Cortes   J., , Deininger   M., , Gratwhohl   A., , Guilhot   F., , Horowitz   M., , Hughes   T., , Kantarjian   H., , Larson   R., , Niederweiser   D., , Silver   R., , Hehlmann   R. . Evolving concepts in the management of chronic myeloid leukemia: Recommendations from an expert panel on behalf of the European LeukemiaNet. . Blood . 2006; ;108: 6 : 1809– 1820 .
    [Google Scholar]
  7. [7]. Baccarani   M., , Cortes   J., , Pane   F., , Niederweiser   D., , Saglio   G., , Apperley   J., , Cervantes   F., , Deininger   M., , Gratwhohl   A., , Guilhot   F., , Hochhaus   A., , Horowitz   M., , Hughes   T., , Kantarjian   H., , Larson   R., , Radich   J., , Simonsson   B., , Silver   R., , Goldman   J., , Hehlmann   R. . Chronic myeloid leukemia: An update of concepts and management recommendations of European LeukemiaNet. . J Clin Oncol . 2009; ;27: 35 : 6041– 6051 .
    [Google Scholar]
  8. [8]. Baccarani   M., , Deininger   M., , Rosti   G., , Hochhaus   A., , Soverini   S., , Apperley   J., , Cervantes   F., , Clark   R., , Cortes   J., , Guilhot   F., , Hjorth-Hansen   H., , Hughes   T., , Kantarjian   H., , Kim   DW., , Larson   R., , Lipton   JH., , Mahon   FX., , Martinelli   G., , Mayer   J., , Müller   MC., , Niederweiser   D., , Pane   F., , Radich   JP., , Rousselot   P., , Saglio   G., , Saußele   S., , Schiffer   C., , Silver   R., , Simonsson   B., , Steegmann   JL., , Goldman   J., , Hehlmann   R. . European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. . Blood . 2013; ;122: 6 : 872– 884 .
    [Google Scholar]
  9. [9]. Gabert   J., , Beillard   E., , van der Velden   VHJ., , Bi   W., , Grimwade   D., , Pallisgaard   N., , Barbany   G., , Cazzaniga   G., , Cayuela   JM., , Cave   H., , Pane   F., , Aerts   JLE., , De Micheli   D., , Thirion   X., , Pradel   V., , Gonzalez   M., , Viehmann   S., , Malec   M., , Saglio   G., , van Dongen   JJM. . Standardization and quality control studies of ‘real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia – a Europe Against Cancer program. . Leukemia . 2003; ;17: 12 : 2318– 2357 .
    [Google Scholar]
  10. [10]. Hughes   TP., , Kaeda   J., , Branford   S., , Rudzki   Z., , Hochhaus   A., , Hensley   ML., , Gathmann   I., , Bolton   AE., , van Hoomissen   IC., , Goldman   J., , Radich   JP. . Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. . N Engl J Med . 2003; ;349: 15 : 1423– 1432 .
    [Google Scholar]
  11. [11]. Bustin   SA. . Developments in real-time PCR research and molecular diagnostics. . Expert Rev Mol Diagn . 2010; ;  10: 6 : 713– 715 .
    [Google Scholar]
  12. [12]. Hughes   T., , Deininger   M., , Hochhaus   A., , Branford   S., , Radich   J., , Kaeda   J., , Baccarani   M., , Cortes   J., , Cross   NCP., , Druker   BJ., , Gabert   J., , Grimwade   D., , Hehlmann   R., , Kamel-Reid   S., , Lipton   JH., , Longtine   J., , Martinelli   G., , Saglio   G., , Soverini   S., , Stock   W., , Goldman   J. . Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. . Blood . 2006; ;108: 1 : 28– 37 .
    [Google Scholar]
  13. [13]. Branford   S., , Fletcher   L., , Cross   NCP., , Müller   MC., , Hochhaus   A., , Kim   DW., , Radich   J., , Saglio   G., , Pane   F., , Kamel-Reid   S., , Lynn Wang   Y., , Press   RD., , Lynch   K., , Rudzki   Z., , Goldman   J., , Hughes   T. . Desirable performance characteristics for BCR-ABL measurement on an international reporting scale to allow consistent interpretation of individual patient response and comparison of response rates between clinical trials. . Blood . 2008; ;112: 8 : 3330– 3338 .
    [Google Scholar]
  14. [14]. White   HE., , Matejtschuk   P., , Rigsby   P., , Gabert   J., , Lin   F., , Lynn Wang   Y., , Bradford   S., , Müller   MC., , Beaufils   N., , Beillard   E., , Colomer   D., , Dvorakova   D., , Ehrencrona   H., , Goh   HG., , El Housni   H., , Jones   D., , Kairisto   V., , Kamel-Reid   S., , Kim   DW., , Langabeer   S., , Ma   ESK., , Press   RD., , Romeo   G., , Wang   L., , Zoi   K., , Hughes   T., , Saglio   G., , Hochhaus   A., , Goldman   J., , Matcalfe   P., , Cross   NCP. . Establishment of the first World Health Organization International Genetic Reference Panel for quantitation of BCR-ABL mRNA. . Blood . 2010; ;116: 22 : e111– e117 .
    [Google Scholar]
  15. [15]. Branford   S., , Cross   NCP., , Hochhaus   A., , Radich   J., , Saglio   G., , Kaeda   J., , Goldman   J., , Hughes   T. . Rationale for the recommendations for harmonizing current methodology for detecting BCR-ABL transcripts in patients with chronic myeloid leukaemia. . Leukemia . 2006; ;20: 11 : 1925– 1930 .
    [Google Scholar]
  16. [16]. Beillard   E., , Pallisgaard   N., , van der Velden   VHJ., , Bi   W., , Dee   R., , van der Schoot   E., , Delabesse   E., , Macintyre   E., , Gottardi   E., , Saglio   G., , Watzinger   F., , Lion   T., , van Dongen   JJM., , Hokland   P., , Gabert   J. . Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using ‘real-time’ quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR) – a Europe against cancer program. . Leukemia . 2003; ;17: 12 : 2474– 2486 .
    [Google Scholar]
  17. [17]. Branford   S., , Hughes   T. . Detection of BCR-ABL mutations and resistance to imatinib mesylate. . Methods Mol Med . 2006; ;125: : 93– 106 .
    [Google Scholar]
  18. [18]. Gerrard   G., , Mudge   K., , Stewart   R., , Foskett   P., , Stevens   D., , Khorashad   JS., , Szdio   R., , Rezvani   K., , Marin   D., , Reid   A., , Apperley   J., , Goldman   J., , Foroni   L. . Duplex quantitative PCR for molecular monitoring of BCR-ABL1-associated hematological malignancies. . Am J Hematol . 2011; ;86: 3 : 313– 315 .
    [Google Scholar]
  19. [19]. Foroni   L., , Wilson   G., , Gerrard   G., , Mason   J., , Grimwade   D., , White   HE., , Gonzalez de Castro   D., , Austin   S., , Awan   A., , Burt   E., , Clench   T., , Farruggia   J., , Hancock   J., , Irvine   AE., , Kizilors   A., , Langabeer   S., , Milner   BJ., , Nickless   G., , Schuh   A., , Sproul   A., , Wang   L., , Wickham   C., , Cross   NCP. . Guidelines for the measurement of BCR-ABL1 transcripts in chronic myeloid leukaemia. . Br J Haematol . 2011; ;153: 2 : 179– 190 .
    [Google Scholar]
  20. [20]. Al-Dewik   NI., , Jewell   AP., , Yassin   MM., , El-Ayoubi   HR., , Morsi   HM. . Studying the impact of presence of point mutation, insertion mutation and additional chromosomal abnormalities in chronic myeloid leukemia patients treated with imatinib mesylate in the State of Qatar. . Adv Appl Biomed . 2013; ;2013: : 1 . 10.5339/aabio.2013.1 .
    [Google Scholar]
  21. [21]. McNiven   M., , Talaulikar   D. . Establishment of a conversion factor for the Cepheid GeneXpert BCR-ABL assay. . Pathology . 2012; ;44: 1 : 55– 57 .
    [Google Scholar]
  22. [22]. de Lavallade   H., , Apperley   J., , Khorashad   JS., , Milojkovic   D., , Reid   AG., , Bua   M., , Szydlo   R., , Olavarria   E., , Kaeda   J., , Goldman   J., , Marin   D. . Imatinib for newly diagnosed patients with chronic myeloid leukemia: Incidence of sustained responses in an intention-to-treat analysis. . J Clin Oncol . 2008; ;26: 20 : 3358– 3363 .
    [Google Scholar]
  23. [23]. Khalil   SH., , Abu-Amero   KK., , Mohared   FA., , Chaudhri   NA. . Molecular monitoring of response to imatinib (Glivec) in chronic myeloid leukemia patients: Experience at a tertiary care hospital in Saudi Arabia. . Genet Test Mol Biomarkers . 2010; ;14: 1 : 67– 74 .
    [Google Scholar]
  24. [24]. Jain   P., , Kantarjian   H., , Nazha   A., , O'Brien   S., , Jabbour   E., , Romo   CG., , Pierce   S., , Cardenas-Turanzas   M., , Verstovek   S., , Borthakur   G., , Ravandi   F., , Quintas-Cardama   A., , Cortes   J. . Early responses predict better outcomes in patients with newly diagnosed chronic myeloid leukemia: Results with four tyrosine kinase inhibitor modalities. . Blood . 2013; ;121: 24 : 4867– 4874 .
    [Google Scholar]
  25. [25]. Marin   D., , Ibrahim   AR., , Lucas   C., , Gerrard   G., , Wang   L., , Szydlo   RM., , Clar   RE., , Apperley   JF., , Milojkovic   D., , Bua   M., , Pavlu   J., , Paliompeis   C., , Reid   A., , Rezvani   K., , Goldman   J., , Foroni   L. . 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: 3 : 232– 238 .
    [Google Scholar]
  26. [26]. Kim   D., , Hamad   N., , Lee   HG., , Kamel-Reid   S., , Lipton   JH. . BCR/ABL level at 6 months identifies good risk CML subgroup after failing early molecular response at 3 months following imatinib therapy for CML in chronic phase. . Am J Hematol . 2014; ;89: 6 : 626– 632 .
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.5339/connect.2014.24
Loading
/content/journals/10.5339/connect.2014.24
Loading

Data & Media loading...

  • Article Type: Research Article
Keyword(s): ABL1 , BCR-ABL1 , CML , Imatinib Mesylate (IM) and RT-qPCR
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error