Differences of Bone Marrow Features and BCR-ABL Variants in Chronic Granulocytic Leukemia Post Tyrosine Kinase Inhibitor Therapy

Wivina Riza Devi, M Darwin Prenggono, Purwanto AP, Imam B

Abstract


Chronic Granulocytic Leukemia (CGL) occurs due to chromosomal translocation (9;22) known as Philadelphia chromosome. p210 BCR-ABL1 oncogenes are classified into b2a2 and b3a2 transcripts which possibly lead to different clinical manifestations and response to therapy. This study was aimed to prove that there is a difference of bone marrow features and BCR-ABL between remissive and resistant CGL after Tyrosine Kinase Inhibitor (TKI) therapy. This research was an observational study with a cross-sectional design carried out at Ulin Hospital Banjarmasin on 32 subjects. BCR ABL was detected by using PCR and bone marrow features were assessed by using bone marrow aspiration technique. The difference of bone marrow features and BCR-ABL variants was analyzed by using T-test (p < 0.005) and Chi-Square (p < 0.005), respectively. There was a difference of BCR-ABL variants with p=0.091 and characterized by M:E ratio (p=0.124), myeloblast count (p=0.063), and eosinophil count (p=0.055). In addition, there was a difference of bone marrow cellularity (p=0.000) and basophil count (p=0.016) between remissive CGL and resistant CGL patients. There was no difference of BCR ABL variants, myeloblast count and eosinophil count between remissive CGL and resistant CGL patients. However, there was different of bone marrow cellularity and basophil count between remissive CGL and resistant CGL patients.


Keywords


CGL, BCR-ABL variants, bone marrow

References


Reksodiputro H, Tadjoedin H, Supandiman I, Supandiman I, Acang N, et al. Epidemiology study and mutation profile of patients with chronic myeloid leukemia (LGK) in Indonesian. Journal of Blood Disorders and Transfusion, 2015; 6(3): 1-13.

Buyukasik Y, Haznedaroglu IC, Ilhan O. Chronic myeloid leukemia: Practical issues in diagnosis, treatment and follow up. Int J of Hematology and Oncology, 2010; 20(2): 1–10.

Christy. Leukemia mielositik kronik. Dalam: Hematology. 1th Ed., WIMI. 2011; 199-206.

Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2016 update on diagnosis, therapy, and monitoring. American Journal of Hematology, 2016; 91(2): 253-255.

Kolibaba KS. Molecular monitoring or response in patients with chronic myeloid leukemia. Managed Care. 2013; 40-58.

Bilen Y, Erden F. Hematologic, cytogenetic and molecular responses to imatinib therapy for chronic myeloid leukemia: A single-center experience in Turkey. Turk J Med Sci, 2012; 42(1): 31-38.

Hasford J, Baccarani M, Hoffmann V. Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with LGK on imatinib treatment: the EUTOS score. The American Society of Hematology, 2011; 118(3): 686-690.

Usman M, Syed NN, Kakepoto GN, Adil SN, Khursid IA. Chronic phase chronic myeloid leukemia: Response of imatinib mesylate and significance of SOCAL score, age and disease duration in predicting the hematological and cytogenetic response. JAPI, 2007; 56: 103-181.

Sauβele S, Richter J, Hochhaus A, Mahon F-X. The concept of treatment-free remission in chronic myeloid leukemia. Macmillan Publishers Limited, Leukemia, 2016; 30: 1638-47.

Baccarani M, Cortes J, Pane F, Niederwieser D, Saglio G et al. Chronic myeloid leukemia: An update of concepts and management recommendations of European Leukemia. Net. J of Clin Oncol, 2009; 6041-51.

Apperley JF. Part I: Mechanisms of resistance to imatinib in chronic myeloid leukemia. Lancet Oncology, 2007; 8: 1018-29.

Liesveld JL, Lichtman MA. Chronic myelogenous leukemia and related disorders. Dalam: William Hematology. 9th Ed., New York, Mc Graw Hill. 2010; 1437-73.

Fausel C. Targeted chronic myeloid leukemia therapy: Seeking cure. Supplement to Journal of Managed Care Pharmacy. 2007; 13(8): S8-S12.

Wang W, Cortes JE, Tang G, Khoury JD, Bueso Ramos SC, et al. Risk stratification of chromosomal abnormalities in chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy. The American Society of Hematology, 2016; 2742-49.

Hoffbrand AV, Pettit JE, Vyas Paresh. Chronic myeloid leukemias and myelomonocytic/myeloproliferative disorder. Dalam: Color atlas of clinical hematology. 4th Ed., Philadelpia, Mosby Elsevier, 2009; 233-246.

Cortes J, Cardama AQ, Kantarjian HM. Monitoring molecular response in chronic myeloid leukemia. Willey Online Library. PMC 2016 Aug 1. 2010; 1113-20.

Hanfstein B, Lausaker M, Hehlmann R, Saussele S, Erben P, et al. Distinct characteristics of e13a2 versus e14a2 BCR-ABL, driven chronic myeloid leukemia under first-line therapy with imatinib. Haematologica, 2014; 99(9): 1441 – 46.

Al-Achkar W, Moassass F, Youseff N, Wafa A. Correlation of p210 BCR-ABL transcript variant with clinical, parameters and disease outcome in 45 chronic myeloid leukemia patients. J BUON, 2016; 21(2): 444 – 449.

Deb P, Chakrabarti P, Chakrabarty S, Aich R, Nath U, Ray SS, Chaudhuri U. 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, 2014; 35(1): 26 – 30.

Hughes TP, Ross DM. Moving treatment-free remission into mainstream clinical practice in CML. The American Society of Hematology, 2016; 128(1): 17–23.

Ren R. Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukemia. Nature Reviews Cancer, 2015; 5: 172 – 180.

Aleman JO, Farooki A, Girotra M. Effects of tyrosine kinase inhibition on bone metabolism: untargeted consequences of targeted therapies. Society for Endocrinology. 2014; R247 – R259.

Hasserjian R, Boeklin F, Parker S, Chase A, Dhar S, et al. ST1571 (imatinib mesylate) reduces bone marrow cellularity and normalizes morphologic features irrespective of cytogenetic response. Hematopathology American Journal of Clinical Pathology, 2012; 117: 360 – 367.

Cotelingan JD. Bone marrow biopsy: Interpretive guidelines for the Surgical Pathologist. Advances in Anatomic Pathology, 2003; 10(1): 8–26.

May P.C, Khorashod J.S, Alitian M, Petotti D, Reid A.G. The genetic of chronic myelogemous leukemia in the genetic basis of haematological cancers. 1st Ed., London, Willey, 2016; 312 – 338.

Bain BJ, Clark DM, Wilkins BS. The normal bone marrow. Dalam: Bone marrow pathology. 4th Ed., London, Wiley-Blackwell, 2013; 1-51.

Lucas CM, Harris RJ, Glannoudis A, Davies A, Knight K et al. Chronic myeloid leukemia patients with the e13a2 BCR-ABL fusion transcript have inferior response to imatinib compared to patients with the e14a2 transcript. Hematologica Journal, 2009; 94(10): 1362-67.

Srinivas BH, Paul TR, Uppin SG, Uppin MS, Jacob RT, Raghunadharao D. Morphologic changes in the bone marrow in patients of Chronic Myeloid Leukemia (CML) treated with imatinib mesylate. Indian J Hematol Blood Transfus, 2012; 28(3): 162 – 169.

Joshi S, Sunita P, Deshmukh C, Gujral S, Amre P, Nair CN. Bone marrow morphological changes in patients of chronic myeloid leukemia treated with imatinib mesylate. Indian Journal of Cancer, 2008; 45(2): 45-49.

Sunita JS, Joshi S, Desmukh C, Gujral S, Amre P, Nair CN. Bone marrow morphological changes in patients of chronic myeloid leukemia treated with imatinib mesylate. Indian Journal of Cancer, 2008; 45(2): 45 – 49.

Machado MP, Tomaz JP, Metze IL, Souca CA, Vigorito AC, Delamain MT, et al. Monitoring of BCR-ABL levels in chronic myeloid leukemia patients treated with imatinib in the chronic in the chronic phase-the importance of a major molecular response. Rev Bras Hematol Hemoter, 2011; 33(3): 211 – 5.




DOI: http://dx.doi.org/10.24293/ijcpml.v26i2.1457

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