Abstract
Background: Analysis of Philadelphia (Ph) chromosome, a hallmark of chronic myeloid leukemia (CML) plays an important role in disease monitoring of the targeted drug Imatinib. Apart from Ph, genomic imbalances such as additional chromosomal abnormalities (ACAs) of major route occur during transformation of the disease and show negative impact on prognosis. Objective: The present study was carried out to investigate frequencies of ACAs, genomic deletions, complex Ph variants and their prognostic influences in a large cohort of newly diagnosed CML-CP (chronic phase) and CML-AP/BP (accelerated/blast phase). Material & Methods: Retrospective, single institutional study on 1367 cases of CML-CP and 82 cases of CML-AP/BP between 2009 and 2015, using conventional cytogenetics along with fluorescence in situ hybridization. Results: Of the 1367 patients in CML-CP, 1041 patients who completed 12 - 18 months of Imatinib therapy showed complete cytogenetic remission (CCyR) rates of 76% and 82% at 12 and 18 months respectively. Imatinib induced 81% and 33% CCyR in CML-AP and CML-BP respectively. Frequencies of ACAs in CML-CP, AP and BP were 2%, 27% and 67% respectively. Patients in chronic and AP/BP phase with ACAs showed resistance to Imatinib (p p p < 0.210 respectively). In a cohort of 112 patients in CCyR, development of new clonal abnormalities, more frequently trisomy 8 was detected in Ph negative clone. Conclusion: Our data demonstrated that Imatinib as a frontline therapy had significantly improved management of CML. However, ACAs play an important role in resistance to Imatinib, both in chronic and acute phase, which may limit sole ABL targeted therapy.
Highlights
Chronic myeloid leukemia (CML) is a pleuripotent stem cell neoplasm that occurs with an incidence of 0.8 - 2.2 per 100,000 in adult men and 0.6 - 1.6 per 100,000 in adult women [1]
The frequencies of standard t(9;22), complex variant Ph and genomic deletions were in the similar range in a cohort of 1041 out of total 1367 chronic myeloid leukemia (CML)-CP cases, who were evaluated for Imatinib response (Table 1)
Our study indicates that trisomy 8 is common in Ph negative clone in CML in complete cytogenetic remission (CCyR) achieved by Imatinib and that has no impact on clinical outcome [18] [36] [40]
Summary
Chronic myeloid leukemia (CML) is a pleuripotent stem cell neoplasm that occurs with an incidence of 0.8 - 2.2 per 100,000 in adult men and 0.6 - 1.6 per 100,000 in adult women [1]. Acquisition of additional chromosomal abnormalities (ACAs) is one of the important features of genomic imbalances which occur during transformation of the disease from chronic phase to accelerated/blast phase in CML [12]-[15]. Conventional cytogenetics along with fluorescence in situ hybridization (FISH) are gold standard tools for identification of t(9;22), evaluation of additional chromosomal abnormalities apart from Ph, and confirmation of BCR-ABL1 fusion in CML cases with variant, masked Ph, cryptic insertion of BCR-ABL1 and genomic deletions [21]-[25]. In a cohort of 112 patients in CCyR, How to cite this paper: Amare, P.S.K., et al (2016) Characterization of Genomic Events Other than Ph and Evaluation of Prognostic Influence on Imatinib in Chronic Myeloid Leukemia (CML): A Study on 1449 Patients from India. ACAs play an important role in resistance to Imatinib, both in chronic and acute phase, which may limit sole ABL targeted therapy
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