t(8;9) (p22;p24) and i(17q) in therapy related myeloid neoplasms

Background Therapy-related myeloid neoplasms (t-MN) are clonal hematopoietic stem cell disorders arising as a late complication following radiation and/or cytotoxic therapy (chemotherapy with alkylating agents or topoisomerase II inhibitors) administered for a primary malignant condition, organ transplant or autoimmune diseases 1 . The term ‘therapy-related’ leukemia is descriptive and is based on a patient’s history of exposure to cytotoxic agents. So, t-MNs are realized and categorized according to the primary treatment and the corresponding genetic and molecular lesions 2 . Translocations involving the JAK2 locus have an oncogenic significance in hematological malignancies. One of these translocation is t(8;9) (p22;p24) which results in human autoantigen pericentriolar material gene 1-Janus activated kinase 2 gene (PCM1-JAK2) fusion gene 3 . Also, Isochromosome 17q is a cytogenetic abnormalities detected in several hematological disorders. It leads to characteristic morphologic features such as pseudo-Pelger-Huet neutrophils and small hypolobated megakaryocytes 4 .We aimed in this study to detect the frequency of t(8;9) (p22;p24) and i(17q) by fluorescent in situ hybridization in the two sub-types of therapy related myeloid neoplasms (t-MDS/t-AML) and also determine the association of t(8;9) and i(17q) with type of therapy, time of exposure and prognostic criteria. Patients and methods A cross–sectional analytic study included 73 t-MN patients and 66 patients with newly diagnosed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), who were tested for t(8;9) and i(17q) by fluorescent in situ hybridization technique. At least 200 metaphases were analyzed for each patient. Results Translocation (8;9) and i(17q) were detected only in cases of t-MDS (15.8 and 7.0%, respectively) and de novo AML cases (5.9 and 15.7%, respectively) with no significant difference between the four studied groups t-MDS, t-AML, de novo AML and MDS. Primary malignancies in t(8;9) positive t-MDS patients were Ewing’s sarcoma, non-hodjkin lymphoma (NHL), AML M4 and T ALL which is the most frequent one. While primary malignancy in i(17q) positive t-MDS was T-acute lymphoblastic leukemia (T-ALL). Alkylating agents and plant alkaloids were the only implicated therapy in patients with t-MN and positive either for t(8;9) or i(17q). Concerning latency period, there is a significant difference between positive and negative cases of t(8;9) ( P <0.001) with being shorter latency in positive cases (median 5 months). However, during comparing the latency period between positive and negative cases of i(17q), there is no significant difference between two groups ( P <0.697) with being shorter latency in negative cases (median 5 months). Conclusion In conclusion, to the best of our knowledge, the present study is the first to report the frequency of t(8;9) and i(17q) in a relatively large number of t-MN cases. Both t(8;9) (p22;p24) and i 17q are uncommon mutations in t-MN and had been detected only in cases of t-MDS and these cases were associated with heterogenous clinical course. However, the detection of PCM1-JAK2 fusion gene in t-MN cases has clinical importance as there may be some response to tyrosine kinase inhibitors. Further studies are recommended to ensure either that t(8;9) (p22;p24) and i 17q are parts of oncogenic events that precede the primary malignancy or sequels of primary malignancy pathogenesis and/or therapy leads to t- MN.