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Mutations of the fms-like tyrosine kinase 3 (FLT3) gene located at chromosome 13q12, alone or in combination with other oncogene mutations, occur in approximately 40% of cases of acute myeloid leukaemia (AML).1–3 Two major types of FLT3 mutations have been identified: (1) internal tandem duplication within the juxtamembrane domain; and (2) mutations affecting codons 835 or 836 of the second tyrosine kinase domain.1 Internal tandem duplications of FLT3 are known to be associated with a poorer prognosis. The t(12;13)(p13;q12) has been reported in a few cases of AML, involving ectopic expression of the homeobox gene CDX2 at chromosome 13q12.4 ,5 The t(12;13)(p13;q12), resulting in a FLT3/EVT6 fusion gene, has not been reported in AML.
We report a case of AML that initially was associated with an internal tandem duplication of FLT3 and subsequently developed t(12;13)(p13;q12) and a FLT3/EVT6 fusion gene associated with FLT3 overexpression. The onset of t(12;13)(p13;q12) was followed by a rapidly progressive disease course and death.
A patient presented with a history of asbestosis, worsening dyspnoea, fever and marked leukocytosis, leading to the patient's referral at a leukaemia clinic in his late 60s. A complete blood count showed haemoglobin of 9.3 g/dl, platelet count of 22 000/mm3 and a white blood cell count of 101 700/mm3 with a differential count of 14.0% neutrophils, 16.0% lymphocytes, 1.0% monocytes and 64% blasts in the blood smear. Bone marrow (BM) aspiration and biopsy were performed. The aspirate smear showed 52% blasts and the biopsy specimen was hypercellular. Flow cytometry immunophenotypic analysis revealed a myeloid immunophenotype; blasts were positive for CD13, CD33, CD49d, CD64 (dim), CD117, CD123, CD184, HLA-DR, myeloperoxidase and TdT (subset), and were negative for CD14, CD19 CD34 and CD56. Conventional cytogenetic analysis revealed a diploid karyotype in all the 20 cells analysed. Molecular testing showed an …