Multimodality Technologies in the Assessment of Hematolymphoid Neoplasms.

Accurate assessment of tissues for hematolymphoid neoplasms requires an integrated multiparameter approach. Although morphologic examination by light microscopy remains the mainstay of initial assessment for hematolymphoid neoplasms, immunophenotypic analysis by immunohistochemistry and/or flow cytometry is essential to determine the pattern of differentiation and to detect minimal disease when morphology is inconclusive. In some cases, immunophenotypic analysis provides additional information for targeted immunotherapy and prognostication. Genotypic studies, including cytogenetics, fluorescence in situ hybridization, DNA microarray, polymerase chain reaction, and/or next-generation sequencing, are also imperative for subclassification of the genetically defined disease entities in the current World Health Organization classification of hematolymphoid neoplasms. Moreover, genotypic studies can establish clonality, stratify patients to determine appropriate treatment, and monitor patients for treatment response.

Peripheral blood monitoring of chronic myeloid leukemia during treatment with imatinib, second-line agents, and beyond.

BACKGROUND: The current study was conducted to compare simultaneously obtained bone marrow (BM) cytogenetics (CTG), peripheral blood (PB) and BM fluorescence in situ hybridization (FISH), and quantitative real-time polymerase chain reaction (Q-PCR) for BCR-ABL1 in monitoring response to treatment with tyrosine kinase inhibitors and homoharringtonine (HHT) in patients with chronic myeloid leukemia (CML). METHODS: PB and BM FISH (n = 112 samples) and/or Q-PCR (n = 132 samples) for BCR-ABL1 were simultaneously obtained in 70 patients with Philadelphia chromosome-positive (Ph+) CML in chronic (68%), accelerated (16%), and blast phase (16%) before the initiation of therapy and during the course of treatment with imatinib (IM) (n = 40 patients), dasatinib (n = 20 patients), nilotinib (n = 4 patients), bosutinib (n = 18 patients), or HHT (n = 4 patients) for patients with newly diagnosed (n = 13 patients), IM-sensitive (n = 34 patients), IM-resistant (n = 30 patients), or IM-intolerant (n = 9 patients) disease. Eighteen patients were found to have Ph+ variants or karyotypic abnormalities in addition to the Ph+. RESULTS: Excellent correlations (r) were observed between PB and BM FISH (r = 0.95) and PB and BM Q-PCR (r = 0.87), as well as BM CTG and PB FISH (r = 0.89) and PB Q-PCR (r = 0.82). This correlation was not affected by the presence of the Ph+ variant or additional chromosomal abnormalities, the presence of ABL1 kinase domain mutations, phase of the disease, or treatment. CONCLUSIONS: PB FISH and Q-PCR appear to be reliable methods with which to monitor response to modern therapy in patients with all phases of CML.

Gene patents: perspectives from the clinical laboratory.

Patents involving human genes, human genetic material, and genotype-phenotype correlations are a reality and are increasingly having a negative effect on the clinical molecular diagnostic laboratory and on patient care. Specifically, gene patents and exclusive licensing of diagnostic testing has a detrimental effect on the quality of laboratory testing, the cost of testing, turnaround time, coordination of care, patient access to testing and the ability to confirm testing at a separate laboratory. In this article, gene patents are discussed from the perspective of a medical director of a molecular diagnostics laboratory, and the effect of such patents on clinical laboratory practice is examined.