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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 …
Contributors All authors participated in the evaluation and management of this case, acquisition of data or analysis and interpretation of data, drafting and revising the manuscript. All authors approve the version of the manuscript being submitted. GL: The first and corresponding author, initiated and conducted the project, reviewed and conducted cytogenetics studies, and wrote the manuscript. RAS: Performed tCGH to identify EVT6/FLT3 rearrangement and edited the manuscript. CEB-R: Performed immunohistochemistry for FLT3 expression, interpreted data and contributed to the writing of the manuscript. JEC. Contributed reagents and to the writing of the manuscript. XIW: Interpreted data and contributed to the writing of the manuscript. LJM: Interpreted data and contributed to the writing of the manuscript. CCY: Interpreted data, contributed figures and contributed to the writing of the manuscript.
Competing interests None.
Ethics approval IRB, UT MD Anderson Cancer center, PA11-0397.
Provenance and peer review Not commissioned; externally peer reviewed.