Article Text

PDF
Correspondence
Double-hit of FLT3 gene in a fatal case of acute myemonocytic leukaemia
  1. Gary Lu1,
  2. Roger A Schulz2,
  3. Carlos E Bueso-Ramos1,
  4. Jorge E Cortes3,
  5. Xiaohong Iris Wang1,
  6. L Jeffrey Medeiros1,
  7. C Cameron Yin1
  1. 1 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  2. 2 Signature Genomic Laboratories, PerkinElmer, Inc., Spokane, Washington, USA
  3. 3 Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  1. Correspondence to Dr Gary Lu, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 350, Houston, TX 77030, USA; gglu{at}mdanderson.org

Statistics from Altmetric.com

Introduction

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.

Case report

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 …

View Full Text

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.