Molecular Diagnostics of Hematological Malignancies

Extract

Molecular diagnostics is a young discipline, and many of its earliest questions revolved around the diagnosis of hematological malignancies. Could identification of leukemias and lymphomas be aided by analysis of their DNA or RNA? The answer is clearly a resounding “Yes”, and we have moved on from simple diagnostic issues to ones of disease classification, prognosis, selection of therapy, and therapeutic efficacy. Along the way, a variety of methods has been employed, from the practically pre-historic (in molecular biology terms) Southern hybridization (sometimes still done with radioactivity!) to cutting edge gene expression arrays and mass spectroscopy. The availability of these tests, however, has not relieved the laboratory scientist from having to correlate the molecular diagnostic laboratory results with the patient's condition and other laboratory findings. Indeed, the hematology arena—rich in data such as morphology, flow cytometry, and several kinds of cytogenetic tests—is perhaps the best example of the need for a comprehensive, integrated approach to diagnosis and treatment. Of necessity, this review downplays many of the clinical and non-genetic aspects of hematological malignancies available elsewhere.^1,2 It focuses on a few of the most common entities (leukemias and lymphomas) illustrative of the variety of testing currently performed and on issues facing the molecular diagnostic laboratory in the near future. The future is likely to be one of increasing laboratory automation and sophistication—commercial kit-based rather than “home brew”, with more extensive gene sequencing and mutation identification, probably incorporating chip technology—until the molecular diagnostic laboratory begins to resemble more closely a contemporary clinical…

ABBREVIATIONS: DNA = deoxyribonucleic acid; mRNA = messenger ribonucleic acid; PCR = polymerase chain reaction; RT-PCR = reverse transcription polymerase chain reaction.