The added values of multiplex reverse transcriptase-PCR followed by mutation screening in the initial evaluation of acute leukemia

Int J Lab Hematol. 2016 Aug;38(4):444-53. doi: 10.1111/ijlh.12521. Epub 2016 Jun 20.

Abstract

Introduction: This study investigates the benefits of using multiplex reverse transcriptase-PCR (RT-PCR) in addition to standard karyotyping during the initial evaluation of acute leukemia.

Methods: A total of 1114 consecutive specimens from patients with acute leukemia were tested using a commercial multiplex RT-PCR kit (HemaVision, DNA Diagnostic). NPM1 and CEBPA mutations were selectively tested in acute myeloid leukemia (AML) patients with multiplex RT-PCR negativity.

Results: In specimens with optimal cytogenetics, the frequency of recurrent translocations was 31.3%, and cryptic translocations were detected in 2.1% of samples. The concordance rate between karyotyping and multiplex RT-PCR was 97.5%. In addition to the established functions, we demonstrated the additional benefits of multiplex RT-PCR, including successful molecular characterization, even in cytogenetically suboptimal specimens (5.7%); detection of submicroscopic aberrations (1.0%); detection of rare but potentially significant translocations or variants (2.5%); selection of AML candidates for mutation analysis (68.3%); and finally exclusion of recurrent translocations in patients with acute lymphoblastic leukemia or mixed phenotype acute leukemia (22.5%).

Conclusion: We reconfirmed the accuracy and reliability of multiplex RT-PCR for diagnosing acute leukemia and demonstrated additional advantages of this system for the initial evaluation of acute leukemia. Thus, multiplex RT-PCR is worth considering in diagnostic testing of acute leukemias.

Keywords: Multiplex RT-PCR; mutation screening; rare aberrations; submicroscopic translocations; suboptimal cytogenetics.

MeSH terms

  • Acute Disease
  • CCAAT-Enhancer-Binding Proteins / genetics
  • Genetic Testing / methods*
  • Humans
  • Leukemia / diagnosis*
  • Leukemia / genetics
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / genetics
  • Mutation
  • Nuclear Proteins / genetics
  • Nucleophosmin
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction*
  • Translocation, Genetic

Substances

  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, human
  • NPM1 protein, human
  • Nuclear Proteins
  • Nucleophosmin