Original Article Karyotypic and fluorescent in situ hybridization study of the centromere of chromosome 7 in secondary myeloid neoplasms Roberta Sandra da Silva Tanizawa1 Cristina Aiko Kumeda1 Raymundo Soares de Azevedo Neto2 Aline de Medeiros Leal1 Patrícia de Barros Ferreira1 Elvira Deolinda Rodrigues Pereira Velloso1 1Cytogenetics Laboratory, Serviço de Hematologia do Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo – USP, São Paulo, SP, Brazil 2Pathology Service, Faculdade de Medicina, Universidade de São Paulo – USP, São Paulo, SP, Brazil Conflict-of-interest disclosure: The authors declare no competing financial interest Submitted: 3/13/2011 Accepted: 9/5/2011 Corresponding author: Roberta Sandra da Silva Tanizawa Laboratório de Citogenética Av. Dr. Enéas de Carvalho Aguiar, 155 1º andar, sala 30 – Cerqueira César 05403-000 – São Paulo, SP, Brazil Phone: 55 11 3061-5544 R-312 robertatani@uol.com.br www.rbhh.org or www.scielo.br/rbhh DOI: 10.5581/1516-8484.20110117 Background: Secondary myeloid neoplasms comprise a group of secondary diseases following exposure to myelotoxic agents or due to congenital diseases. The improvement of anticancer agents and immunosuppressive drugs seem to be associated with an increased incidence of secondary myeloid neoplasms. Karyotyping of bone marrow is essential for diagnosis and prognosis. Previous use of alkylating agents and radiation are associated with clonal abnormalities such as recurrent unbalanced -5/5q-, -7/7q- and complex karyotypes, whereas topoisomerase-II inhibitors lead to changes such as the balanced 11q23 rearrangement, t(8;21), t(15;17) and inv(16). Objective: To study the clinical and cytogenetic data of patients with secondary myeloid neoplasms who took antineoplastic and/or immunosuppressive drugs or progressed from aplastic anemia. Methods: The clinical and cytogenetic characteristics of 42 patients diagnosed with secondary myeloid neoplasms in one institution were retrospectively evaluated. Of these, 25, 11 and 6 patients had had oncological diseases, aplastic anemia and other diseases, respectively. Conventional cytogenetic and FISH analyses were performed for monosomy 7. Results: The cytogenetic study was conclusive in 32 cases with 84.4% of clonal abnormalities. Monosomy 7 and complex karyotypes were present in 44.4% and 37%, respectively. A high prevalence of unbalanced abnormalities (96.3%) was observed. Monosomy 7 was more prevalent in patients with myelodysplastic syndromes/myeloid neoplasms after aplastic anemia (66.6%). The median survival after diagnosis of myeloid neoplasms was only 5.7 months. Normal cytogenetics was associated to better survival (p-value = 0.03). There was a slightly worse trend of survival for patients with complex karyotypes (p-value = 0.057). Abnormal karyotype was an independent risk factor for poor survival (p-value = 0.012). Conclusion: This study enhances the importance of cytogenetic analysis of patients at the time of diagnosis of secondary myeloid neoplasms. Keywords: Cytogenetic analysis; Myelodysplastic syndromes; Leukemia, myeloid Introduction The myelodysplastic syndromes (MDS), acute myeloid leukemias (AML) and secondary myeloproliferative syndromes (MPS) constitute a group of myeloid neoplasias (MNs) which result from exposure to risk factors such as chemotherapy and radiotherapy, acquired aplastic anemia associated with immunosuppression and congenital diseases.(1-5) A cytogenetic study of the bone marrow, fundamental for the characterization of the secondary MNs, provides essential information for the diagnosis and prognosis of the disease. Between 80 and 95% of patients with MDS/MN present abnormal and frequently complex karyotypes (an average of 5.3 abnormalities per case). Chromosome 7 monosomy is the commonest alteration in patients with secondary MN after aplastic anemia (AA).(6) It is estimated that 10-20% of myeloid neoplasia cases are secondary to the use of chemotherapeutic agents and/or radiotherapy.(5) The progress of therapeutic regimens used to treat primary neoplasias, as well as the new conditions of autologous hematopoietic stem cell transplantations (HSCT), have led to an increase in the rate of therapy-related myeloid neoplasia (MN-t) cases.(7) Some patterns of chromosomal abnormalities are recurrent after exposure to cytotoxic agents. The previous use of alkylating agents/radiation can favor the development of MN-t, which is usually associated with cytopenia and dysplasia and often involves unbalanced clonal genetic alterations including monosomies or deletions of chromosomes 5 and/or 7, and complex karyotypes with numerous marker chromosomes that may progress to point alterations in the P53 and AML1 genes. Previous use of topoisomerase II inhibitors (etoposide, anthracyclines) is usually associated with the development of AML, frequently with Rev Bras Hematol Hemoter. 2011;33(6):425-31 425