Deletion of derivative ABL, BCR or ABL-BCR fusion gene is associated with shorter disease free survival in CML patients

Abstract

Chronic myeloid leukemia (CML) is characterized by formation of the BCR/ABL fusion gene, usually as a consequence of the Philadelphia (Ph) translocation between chromosomes 9 and 22. However, deletions of the derivative 9 chromosome [der (9)] in10 - 15% of CML patients with a standard Ph translocation as well as > 30% of CML patients with a variant Ph translocation may have verse prognosis. The study shed light on prognostic effect of submicroscopic deletions of the derivative chromosome 9 in CML in untreated patients and their follow up samples to correlate with survival. The study included blood and/or bone marrow (BM) samples of 65 untreated CML patients (PT) and 76 follow-up samples classified as cytogenetic responders (CyR, n =42), non-cytogentic responders (NCyR, n = 25) and partial cytogenetic responder (PCyR, n = 9). Karyotype analysis was performed on metaphases obtained through short term cultures of BM and blood. Detection of BCR-ABL fusion gene was performed using dual colour dual fusion (D-FISH) translocation probes. Data were analysed using SPSS statistical software. CyR showed significantly elevated hemoglobin (p = 0.0001) and decreased in total WBC (p = 0.0001) and Platelet counts (p = 0.0001) as compared to pretreatment levels. 61.5, 30.8 and 7.7% of the PT showed CyR, NCyR and PCyR respectively. Kaplan-Meier survival curve showed the patient with CyR, NCyR and PCyR as well as patients with different stage of the disease did not find difference in survival time. ABL-BCR deletion on derivative 9 was seen in 9.2% of PT, while ABL-BCR, ABL or BCR deletion on derivative 9 was found around 7.7% of PT. Patients with deletion of ABL-BCR on derivative 9 and deletion of ABL or BCR and/or ABL-BCR on derivative 9 have significantly reduced survival (log rank = 14.54; p = 0.001) than non deleted patients. Deletion in ABL, BCR orABL-BCR on derivative 9 could predict over the survival of all CML patients. Key words: CML, BCR-ABL fusion Gene, FISH, derivative 9 deletion.