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Artigo / Article Frequency of the BCR/ABL rearrangements and associated alterations detected by FISH during monitoring of patients taking imatinib mesylate in isolation Freqüência do rearranjo BCR/ABL e alterações associadas detectadas por FISH no monitoramento de pacientes em uso exclusivo do mesilato de imatinibe

This study reports an adult AML-M4 patient with atypical chromosomal aberrations present in all dividing bone marrow cell at diagnosis: t(1;8)(p32.1;q24.2), der(9)t(9;10)(q22;?), and ins(19;9)(p13.3;q22q34) that may have originated transcripts with leukemogenic potential. Acute non-lymphocytic or myelogenous leukemia (ANLL or AML) represents a hematopoietic malignancy characterized by abnormal cell proliferation and stalled differentiation leading to the accumulation of immature cells in the marrow itself, in peripheral blood and eventually in other tissues. Primary chromosomal abnormalities in AML are highly specific and considered to be associated with leukemic transformation, whereas secondary changes are less specific and probably contribute to disease progression. As reviewed by Chen and Sandberg. (2002), the common chromosomal abnormalities in the acute myelomonocytic leukemia FAB (French-American-British Cooperative Group) type M4 include monosomy 5 or del(5q), monosomy 7 or del(7q), trisomy 8, t(6;9) (p23;q34), and rearrangements involving the Mixed Lineage Leukemia (MLL) gene mapped at 11q23 [del(11) (q23); t(9;11)(p22;q23), t(11;19)(q23;p13)], and Core Binding Factor B (CBFβ) mapped at 16q22 [del(16)(q22), inv(16)(p13q22), t(16;16)(p13;q22)]. Less frequently, trisomy 4, trisomy 22, t(8;21)(q22;q22) and rearrangements with breakpoints in 3q21, 3q26, 8p11, 11p15 and 11q13 have also been reported in FAB M4 type patients

Artigo IntroduçãoO câncer é uma doença genética (1) e as mutações que lhe dão origem podem ser hereditariamente transmitidas pela linhagem germinativa ou adquiridas nos tecidos somáticos (2). Tais alterações no DNA podem ser causadas por fatores internos como, por exemplo, defeitos nos mecanismos de reparo ou replicação, ou externos, como radiação ionizante, mutagênicos químicos e biológicos (3).Muitas evidências sugerem que a maioria dos neoplasmas são de natureza clonal, ou seja, surgem da expansão de uma única alteração celular inicial. Divisões celulares sucessivas podem produzir subpopulações de células filhas com alterações genéticas adicionais, em função de uma instabilidade genômica, que podem fornecer vantagens seletivas e culminar na aquisição da malignidade. Algumas destas alterações podem dar às células uma vantagem de

Alterações cromossômicas e freqüência do rearranjo gênico BCR/ABL ao diagnóstico, tratamento com mesilato de imatinibe e após transplante de medula óssea em leucemia mielóide crônica Chromosomal alterations and frequency of the BCR/ABL gene rearrangement at diagnosis of chronic myeloid leukemia, treatment with imatinib mesylate followed by bone marrow transplantation

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ABSTRACT. Investigation of the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myeloid leukemia patients is essential to predict prognosis and survival. In 20 patients treated at the Bone Marrow Transplantation Unit of São José do Rio Preto (São Paulo, Brazil), we used fluorescence in situ hybridization (FISH) to investigate the frequency of cells with BCR/ABL rearrangement at diagnosis and at distinct intervals after allo-HSCT until complete cytogenetic remission (CCR). We investigated the disease-free survival, overall survival in 3 years and transplant-related mortality rates, too. Bone marrow samples were collected at 1, 2, 3, 4, 6, 12, and 24 months after transplantation and additional intervals as necessary. Success rate of the FISH analyses was 100%. CCR was achieved in 75% of the patients, within on average of 3.9 months; 45% patients showed CCR within 60 days after HSCT. After 3 years of the allo-HSCT, overall survival rate was 60%, disease-free survival was 50% and the transplant-related mortality rate was 40%. The study demonstrated that the BCR-ABL FISH assay is useful for followup of chronic myeloid leukemia patients after HSCT and that the clinical outcome parameters in our patient cohort were similar to those described for other bone marrow transplantation units.