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Study on Mutation Resistance to Imatinib in Chronic Myeloid Leukemia Patients from West India
Science Journal of Analytical Chemistry
Volume 9, Issue 1, March 2021, Pages: 1-17
Received: Mar. 6, 2020; Accepted: Apr. 1, 2020; Published: Jan. 4, 2021
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Ankit Darji, Department of Pharmacy, Hemchandracharya North Gujarat University, Patan, Gujarat, India
Praful Bharadia, L. M. College of Pharmacy, Navrangpura, Ahmedabad, Gujarat, India
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Imatinib is a type of protein tyrosine kinase inhibitor which inhibits the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome i.e. the BCR-ABL tyrosine kinase, abnormality in CML patient. The aim of the study is to assess the response of imatinib in CML patients and to observe resistance to imatinib. Study was performed at Ahmedabad, Gujarat, India. Dose of 400, 600, 800 mg of Imatinib was found to be prescribed to all patients during the study. Comparison of laboratory parameters and PCR data were done after measurement by RT-PCR method. Total 256 patients with CML were enrolled in the study. 196 patients had completed study as per protocol. 38 patients were newly diagnosed whereas 158 patients were already diagnosed with CML. 89.29% (n = 175) of patients achieved complete haematological response, Complete MolR were achieved in n = 41 at 6th months, n = 1 at 12th month & 18th month and no patient was found with none CyR out of 196 patients; no patient were found with minimal CyR at 6th month, 2 patient were at 12th month and 3 patients were at 18th month. Mean PCR value (BCR-ABL/ABL ratio) in patient was found 0.245±1.16 at Day 0, 0.824±1.51 at 6th month, 4.086±9.58 at 12th month and 6.713±11.32 at 18th month visit. In conclusion, it was observed that resistance to imatinib might be developed within an average time of 12 months in the patients due to which survival rate was drastically reduced.
Cancer, CML, Imatinib, BCR-ABL, Mutation, Resistance
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Ankit Darji, Praful Bharadia, Study on Mutation Resistance to Imatinib in Chronic Myeloid Leukemia Patients from West India, Science Journal of Analytical Chemistry. Vol. 9, No. 1, 2021, pp. 1-17. doi: 10.11648/j.sjac.20210901.11
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Hejmadi M, Introduction to Cancer Biology, 1st edn, Ventus Publishing, 2010, pp 6-42.
National cancer
Kuby J, Goldsby RA, Kindt TJ, Obourne BA, Immunology, 4th edn, W. H Freeman and Company, 2000, pp 501-502.
Knowles MA, Selby PJ, Introduction to Cellular and Molecular Biology of Cancer, 4th edn, Oxford University Press, 2005, pp 15-289.
NPTEL – Chemistry – Bio-Organic Chemistry of Natural Enediyne Anticancer Antibiotics, Joint initiative of IITs and IISc – Funded by MHRD, Page 1-64.
N. L. Harris et al., A Revised European-American Classification of Lymphoid Neoplasms: A Proposal From the International Lymphoma Study Group, Blood, Sep 1994; 84 (5); pp 1361-1392.
Druker BJ, Talpaz M, Resta DJ, et al. “Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia.” N. Engl. J. Med. 2001, 344, 31-37.
Kantarjian H, Sawyers C, Hochhaus A, et al, “Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia.” N. Engl. J. Med. 2002, 346, 645-652.
Gschwind H, Pfaar U, Waldmeier F, Zollinger M, Sayer C, Zbinden P, et al, “ Metabolism and disposition of imatinib mesylate in healthy volunteers.” DMD. 2005, 33, 1503–1512.
Anderson PO, Knoben JE, Troutman WG, Handbook of Clinical Drug Data, 10th edn, McGraw Hill Medical Publishing Division, 2002, pp 266-267.
Tejani S, Sanoski CA, Davis’s Pocket Clinical Drug Reference, 1st edn, F A Davis Company, 2009, pp 141-142.
Deininger M, Buchdunger E, Druker BJ, “The development of imatinib as a therapeutic agent for chronic myeloid leukemia.” Blood. 2005, 105 (7), 2640-2653.
K. Patton and D. C. Borsoff, “Adverse Drug Reactions”, Anaesthesia, 2018, 73 (1), 76–84.
Alan H Turner, Marilyn J Pike and Maureen A Francis, “Haematology what does your blood test mean?, RMIT university”, Edited by: Indu Singh 2008, School of Medical Science 2008, 1-12.
Trevor J. Whitbread, “Clinical Biochemistry”, Abbey Veterinary Services, MSD and the MSD Veterinary Manual, dated 15 Aug 2017.
Bartlett, J. M. S., & Stirling D, “A short history of the polymerase chain reaction. Methods in Molecular Biology”, Methods Mol Biol. 2003; 226; 3-6.
Kleppe K, Ohtsuka E, Kleppe R, Molineux I, Khorana HG, “Studies on polynucleotides. XCVI. Repair replications of short synthetic DNA's as catalyzed by DNA polymerases”, J Mol Biol. 1971; 56 (2); 341-61.
Saiki R. K.; Scharf S., Faloona F., Mullis K. B., Horn G. T., Erlich H. A., Arnheim N., "Enzymatic amplification of betaglobin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia", Science. 1985; 230 (4732); 1350–4.
Erlich, H. A., “PCR technology: principles and applications for DNA amplifications”, Stockton Press 1989, NY. Website:
Gibbs, R. A; DNA Amplification by the Polymerase Chain Reaction. Analytical Chemistry, 1990, 62: 1202-1214.
Arnheim, N; Erlich, H; Polymerase Chain Reaction Strategy. ANNUAL REVIEW OF BIOCHEMISTRY, 1992; VOL. 61. XIV1992: 131-156.
Erlich, H. A; Gelfand, D; Sninsky, J. J. Recent Advances in the Polymerase Chain Reaction. Science, 1991; 252, 5013, 1643-1651.
Moshfeghi K. et al., Hematologic, liver enzymes and electrolytes changes in chronic myeloid leukemia after Imatinib medication; Indian Journal of Cancer, July-September 2015; 52 (3): 305-307.
R. A. Larson, Chronic Myeloid Leukemia; Chronic myeloid leukemia - Cancer Therapy Advisor, 2018;
D. Prihatni et al., Tyrosine Kinase level and White Blood Cells Count in Untreated and Treated Chronic Myelogenous Leukemia Patients with BCR ABL gene; International Journal of Science and Research, July 2016; 5 (7): 1312-1316.
Y. Qin et al., Combination of White Blood Cell Count at Presentation With Molecular Response at 3 Months Better Predicts Deep Molecular Responses to Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia Patients; Medicine, January 2016; 95 (2): 1-9.
U. S. Mogalluru et al., Effect of Imatinib Mesylate on Platelet Aggregation Plat Abnormalities in BCR-ABL + CML Patients; Blood Journal, 2008; 112: 1-4.
A. S. Vornhagen et al., Improvement of platelet dysfunction in chronic myelogenous leukemia following treatment with imatinib: a case report; Journal of Medical Case Reports, 2011; 5: 1-4.
O. M. Akay et al., Platelet Dysfunction in Patients with Chronic Myeloid Leukemia: Does Imatinib Mesylate Improve It?; Turk J Hematol 2016; 33: 127-130.
A. Q. Cardama et al., Tyrosine kinase inhibitor–induced platelet dysfunction in patients with chronic myeloid leukemia; BLOOD, JULY 2009; 114 (2): 261-263.
W. Warit et al., High Prevalence of Platelet Dysfunction Among Patients with Chronic Myeloid Leukemia Receiving Tyrosine Kinase Inhibitors; Blood, 2014; 124: 2781.
M. Radwi et al., Drug-induced immune thrombocytopenia associated with use of tyrosine kinase inhibitor imatinib; Journal of Taibah University Medical Sciences, 2015; 10 (3): 365-368.
A. M. El-Ghammaz et al., Basophil progenitor marker histamine and its relation to the treatment response in Egyptian chronic myeloid leukemia patients; The Egyptian Society of Haematology, 2014; 39 (3): 30-36.
V. F. Furtado et al., Accelerated phase chronic myeloid leukemia: evaluation of clinical criteria as predictors of survival, major cytogenetic response and progression to blast phase; Brazilian Journal of Hematology and Hemotherapy, 2015; 37 (5): 341–347.
M. Anand et al., Chronic myeloid leukemia presenting with absence of basophils and marked dyspoiesis; Indian Journal of Cancer, 2003; 40 (4): 144-147.
P. Valent, The underestimated role of basophils in Ph+ chronic myeloid leukaemia; Eur J Clin Invest., 2018: 1-9.
A. Pardanani, Imatinib therapy for hypereosinophilic syndrome and other eosinophilic disorders; Blood, 2003; 101: 3391-3397.
J. Cortes, Efficacy of imatinib mesylate in the treatment of idiopathic hypereosinophilic syndrome; BLOOD, June 2003; 101 (12): 4714-4716.
K. Cwynarski, Imatinib inhibits the activation and proliferation of normal T lymphocytes in vitro; Leukemia, 2004; 18: 1332–1339.
L. Legros et al., Imatinib Sensitizes T-cell Lymphocytes From Chronic Myeloid Leukemia Patients to FasL-induced Cell Death: A Brief Communication; Journal of Immunotherapy, FEB 2012; 35 (2): 154–158.
P. Rohon et al., Differential Effects of Imatinib and Dasatinib Ima On Immune Effector Cells in Patients with Chronic Myeloid Leukemia (CML); Blood, 2009; 114: 3285.
L. O. Ngolet et al., Pregnancy and Accelerated Phase of Myeloid Chronic Leukemia Treated with Imatinib: A Case Report from a Developing Country; Case Reports in Hematology, 2016: 1-3.
L. Rice, Every Case of Essential Thrombocythemia Should Be Tested for the Philadelphia Chromosome; American Journal of Hematology, 2005; 78: 71–73.
A. Khandelwal et al., Imatinib resistance in chronic myelogenous leukemia: an emerging challenge; International Journal of Basic & Clinical Pharmacology, Oct 2014; 3 (5): 908-911.
C. L. Sawyers et al., Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study; BLOOD, MAY 2002; 99 (10): 3530-3539.
N. Singhal, P. P. Bapsy, K. G. Babu, J. George, Chronic Myeloid Leukemia; JAPI, May 2004; 52: 410-416.
Y. Xu, A. E. Wahner, P. L. Nguyen, Progression of Chronic Myeloid Leukemia to Blast Crisis During Treatment With Imatinib Mesylate; Arch Pathol Lab Med, September 2004; 128: 980-985.
Blastic Myeloid Leukemia, Texas Oncology;, 10/4/2018: 1-6.
R. P. Hasserjian et al., STI571 (Imatinib Mesylate) Reduces Bone Marrow Cellularity and Normalizes Morphologic Features Irrespective of Cytogenetic Response; Am J Clin Pathol 2002; 117: 360-367.
J. Gotlib, J. E. Maxson, T. I. George and J. W. Tyner, The new genetics of chronic neutrophilic leukemia and atypical CML: implications for diagnosis and treatment; BLOOD, Sep 2013; 122 (10): 1707-1711.
S. Duartea, S. C. Pereiraa, E. Rodriguesa, A. Pereira, Concomitant chronic myeloid leukemia and monoclonal B cell lymphocytosis – a very rare condition; Brazilian Journal of Hematology and Hemotherapy, 2017; 39 (2): 167–169.
J. Hoffman, Increased Serum Creatinine Reversible upon Imatinib Discontinuation, Cancer Therapy Advisor, Mar 2016: 1.
E. Vidal-Petiot et al., Imatinib Increases Serum Creatinine by Inhibiting Its Tubular Secretion in a Reversible Fashion in Chronic Myeloid Leukemia; Clinical lymphoma, myeloma & leukemia, Mar 2016; 16 (3): 169-174.
D. Renard, T. Bouillon, P. Zhou, G. Flesch & D. Quinn, Pharmacokinetic interactions among imatinib, bosentan and sildenafil, and their clinical implications in severe pulmonary arterial hypertension; British Journal of Clinical Pharmacology, Jan 2015; 80 (1): 75-85.
H. Kantarjian et al., Improved survival in chronic myeloid leukemia since the introduction of imatinib therapy: a single-institution historical experience; Blood, Mar 2012; 119 (9): 1981–1987.
E. J. Jabbour, J. E. Cortes and H. M. Kantarjian, Resistance to Tyrosine Kinase Inhibition Therapy for Chronic Myelogenous Leukemia: A Clinical Perspective and Emerging Treatment Options; Clin Lymphoma Myeloma Leuk., Oct 2013; 13 (5): 515–529.
P. Gadhia, G. Shastri, E. G. Shastri, Imatinib Resistance and Relapse in CML Patients with Complex Chromosomal Variants; American Journal of Cancer Science, Sep 2015; 4: 43-53.
V. Nardi, M. Azam, G. Q. Daley, Mechanisms and implications of imatinib resistance mtations in BCR-ABL; Current Opinion in Hematology, February 2004; 11 (1): 35-43.
Z. Iqbal, R. T. Siddiqui, J. A. Qureshi & A. M. Khalid, Case study of primary imatinib resistance and correlation of BCR-ABL multiple mutations in chronic myeloid leukemia; Therapy, 2004; 1 (2): 249–254.
R. Aich et al., Incidence of BCR-ABL transcript variants in patients with chronic myeloid leukemia: Their correlation with presenting features, risk scores and response to treatment with imatinib mesylate; Indian Journal of Medical and Paediatric Oncology, Mar 2014; 35 (1): 26-30.
Yu-Yan Hwang et al., Persistent neutropenia in chronic myelogenous leukemia in chronic phase treated with imatinib mesylate; American Journal of Hematology, Feb 2009: 302-305.
E. J. Jabbour, Use of PCR Testing in Chronic Myeloid Leukemia; Clinical Advances in Hematology & Oncology, Dec 2015; 13 (12): 808-810.
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