In previous papers, we reported that additional chromosome abnormalities (ACAs) present at diagnosis in Chronic Myeloid Leukemia (CML) patients, could persist after the disappearance of the Ph during Imatinib therapy, thus demonstrating the secondary origin of the Ph in these cases.1,2 We tried to verify the real incidence and the possible prognostic value of this finding in a larger population of patients. Patients and Methods. Thirty-six patients were the object of this study. Twenty-one were collected among the 506 ones included into three multicentric national trials (CML 021, CML 022, CML 023) of the GIMEMA Working Party (WP) on CML; moreover, 15 more patients, not included in the trials, were collected from 9 of the 54 Cytogenetics Laboratories included in the GIMEMA WP. All of them were treated either initially or during the course of the disease with Imatinib. Karyotypes were performed according to methods described in a previous paper3 and chromosomes were classified according to ISCN 2005.4 Results. Table 1a shows the distribution of the patients according to Sokal Score and their response to Imatinib. We divided the patients into 3 groups: 1) patients in which ACAs persisted after therapy in Ph negative cells; 2) patients in which ACAs were always present together, and disappeared with, the Ph in case of response; 3) patients with the same characteristics of group 2 and no response, with persistence of ACAs together with the Ph. Table 1b shows the type of chromosome abnormalities and their outcomes. Discussion. The persistence of ACA in Ph-negative cells during Imatinib treatment (patients n.1 to n.6) suggests that they occurred as primary events in a genetically unstable cell.1,2 In the other patients, the occurrence of the Ph chromosome was clearly a primary event, further on documented by the detection of metaphases with Ph as the sole abnormality in 5 patients. Moreover, based on the data reported here, we can point out that: 1) The occurrence of ACA as a primary event is a rather unusual phenomenon. 2) Sokal Score maintains its unfavourable prognostic value in patients in which Ph occurs as a primary event and not in those in which it occurs as a secondary one.5,6 3) The type of ACAs may influence the outcome of the disease, possibly inducing resistance to Imatinib due to the activation of different pathways of disease progression.

CHROMOSOME ABNORMALITIES ADDITIONAL TO THE PHILADELPHIA CHROMOSOME AT THE DIAGNOSIS OF CHRONIC MYELOID LEUKEMIA. PATHOGENETIC AND PROGNOSTIC IMPLICATIONS.

CAVAZZINI, Francesco;
2009

Abstract

In previous papers, we reported that additional chromosome abnormalities (ACAs) present at diagnosis in Chronic Myeloid Leukemia (CML) patients, could persist after the disappearance of the Ph during Imatinib therapy, thus demonstrating the secondary origin of the Ph in these cases.1,2 We tried to verify the real incidence and the possible prognostic value of this finding in a larger population of patients. Patients and Methods. Thirty-six patients were the object of this study. Twenty-one were collected among the 506 ones included into three multicentric national trials (CML 021, CML 022, CML 023) of the GIMEMA Working Party (WP) on CML; moreover, 15 more patients, not included in the trials, were collected from 9 of the 54 Cytogenetics Laboratories included in the GIMEMA WP. All of them were treated either initially or during the course of the disease with Imatinib. Karyotypes were performed according to methods described in a previous paper3 and chromosomes were classified according to ISCN 2005.4 Results. Table 1a shows the distribution of the patients according to Sokal Score and their response to Imatinib. We divided the patients into 3 groups: 1) patients in which ACAs persisted after therapy in Ph negative cells; 2) patients in which ACAs were always present together, and disappeared with, the Ph in case of response; 3) patients with the same characteristics of group 2 and no response, with persistence of ACAs together with the Ph. Table 1b shows the type of chromosome abnormalities and their outcomes. Discussion. The persistence of ACA in Ph-negative cells during Imatinib treatment (patients n.1 to n.6) suggests that they occurred as primary events in a genetically unstable cell.1,2 In the other patients, the occurrence of the Ph chromosome was clearly a primary event, further on documented by the detection of metaphases with Ph as the sole abnormality in 5 patients. Moreover, based on the data reported here, we can point out that: 1) The occurrence of ACA as a primary event is a rather unusual phenomenon. 2) Sokal Score maintains its unfavourable prognostic value in patients in which Ph occurs as a primary event and not in those in which it occurs as a secondary one.5,6 3) The type of ACAs may influence the outcome of the disease, possibly inducing resistance to Imatinib due to the activation of different pathways of disease progression.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1401588
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